pets

					 Pets and asthma – what do
we know and what should we
            do?

          Angela Simpson
      University of Manchester
    University Hospital of South
  Manchester NHS Foundation Trust
Cats and Dogs

       • In the U.K. ~16
         million cats and
         dogs
       • 10 million
         children in the UK
         – ~ 7% children
           sensitised to cat
         – ~ 4% children
           sensitised to dog

            Sadeghnejad et al Thorax 2004
             Sensitisation to pets is a risk factor for
                             asthma
                                            1       1.2      1.4   1.6 1.8 2 2.2 2.4 2.6      3.0
        Sensitisation to Allergens
                 House dust mite                                                      *
                              Cat                                                         *
                              Dog                                                 *
                            Pollen                                            *

                      Pet Ownership
                         Dog owner                     *
                     Smoking Status
                            Smoker                       *
                               Sex
                            Female                           *
                                   *p = <0.0001 *p=0.001 - 0.0001 *p=0.05 - 0.001

Simpson, Custovic et al, Clin Exp Allergy 2001; 31:391-399
              Sensitisation to pets is a risk factor
              for hospital admission with asthma

               90
               80
               70
      %        60                                      hopsital
               50                                      admission
               40                                      stable asthma
               30
               20                                      Control
               10
                0
                     cat   dog   mite   Any allergen


Murray et al Thorax 2006
                       Cat
              (Felis domesticus)

• Allergenic activity in
  dander, pelt, saliva,
  serum and urine
• Major allergen Fel d
  1, function unknown,
  present in
  sebaceous and
  salivary glands
• 90% of IgE to cat is
  to Fel d 1
                 Fel d 1

• Concentration 10 fold higher at the
  root than at the tip of car fur
• Cats can produce 3-7 mcg day
• Production under hormonal control
  – levels fall after castration of male cats
  – restored by testosterone treatment
• Can be measured using
  monoclonal antibody based ELISA
                 Dog
           (Canis familiaris)

• Allergenic activity in dander, pelt
  hair and saliva (not urine)
• Major Allergen Can f 1, produced in
  salivary glands
• Accounts for ~ 50% allergenic
  activity
• ~ 80-90% of dog allergic subjects
  have IgE to Can f 1
              All dogs are not equal – but within breed
             differences are as great as between breed
                             differences




The first dog, Bo – a Portuguese Water Dog   Ramadour et al Allergy 2005;60:1060
            Hypoallergenic pets
(‘focused on rare naturally occurring genetic divergences
                    already present’)
              Homes with pets have >100 fold higher
                 allergen levels on surfaces….
   Cat Allergen in Homes With and Without Cats
     Fel d 1 (g/g)
     10000

      1000

       100

         10

          1


       0.06

                    Mattress           Bedroom    Living room          Uphd.
                                        carpet       carpet           furniture
Custovic et al                 Homes with cats   Homes without cats
Thorax 1998;53:602-607
  Airborne Can f 1 in Homes
                   …and
    With and Without Dogs                  in the air
                                                                  3
                       3                         Fel d 1 (ng/m )
   Can f 1 (ng/m )
                                                 100
  100




                                                  10

    10



                                                    1


     1


   0.3                                           0.1




             Without dogs      With dogs                   Without cats   With cats

                                           Custovic et al
                                           Thorax 1998;53:33-38
Custovic et al
Am J Resp Crit Care Med 1997
         Cat Allergens in
        Cat Allergens in Public Places
      Fel d 1 ( g/g)
100



 10



  1



0.1
      Carpets Seats Carpets Seats       Carpet    Seats Mattress Carpets        Seats
         Public         Cinema                     Hotel              School     Public
         Houses                                                                Transport
                  Custovic et al Clin Exp Allergy 1996; 26: 1246-52
…..and the air
Much allergen is carried on small
      respirable particles




    Particle size distribution of Fel d 1 (m)
    We have established that

• Pets are common
• Sensitisation to pets is common
• Sensitisation to pets is a risk factor
  for asthma
• Pet allergen is ubiquitous and
  easily respirable
So who becomes sensitised to pets
     and who gets disease?
 Difficulties of studying pet allergies

• Cannot do randomised controlled trials
• Confounders – pet owners are more
  likely to
  – smoke cigarettes
  – have lower educational status
  – not use day care or breastfeed
• Homes with pets contain more
  endotoxin
• Ownership is subject to recall bias
• Birth cohorts offer best insights
            Cat ownership is a risk factor for
                  sensitisation to cats
                     (in Sweden)

40
                                         50
35
30                                       40
25                              never
                                         30
20                              later                            none
                                early                            <8 mcg/g
15                                       20
                                always                           >8 mcg/g
10
                                         10
5
0                                        0
         cat ownership status                 Fel d 1 exposure




Melen et al, Allergy 2001
                 Or cat ownership is protective
                        (also in Sweden)
          • N>2000 school children living in the
            Arctic circle in Sweden
          • No dust mites
          • 20.6% of the population were atopic,
            13.4% sensitised to cat
          • Ever having lived with a cat was
            protective for
               – cat allergy (OR 0.62, 95% CI 0.47-0.83)
               – asthma (OR 0.56, 95% CI 0.31-0.99)


Perzanowski et al, Am J Respir Crit Care Med 2002
Children in Los Alamos developed a
 ‘modified TH2 response’ at high
        allergen exposures
  Children with cats at birth may get
 sensitised earlier, but those without
          cats soon catch up
• Similar effect seen in
   – Mas-90
   – PIAMA
   – New York
• No difference
  between those
  with/without cats in
   –   Isle of Wight
   –   Tucson CRS
   –   COAST
   –   Children’s Allergy
       Study

                            Simpson PhD thesis 2009
   Exposure outside the home is
            important

• Across Europe, the community
  prevalence of sensitisation to cat
  amongst non-cat owners correlates
  positively with community cat
  ownership rates
  – i.e. more cats in the community
    means more non-cat owners will be
    sensitised
               Dogs may be protective…..

               9
               8
               7
               6
               5                        no dogs
               4                        1 dog
               3                        2 or more dogs
               2
               1
               0
                         % sensitised


Ownby et al, JAMA 2002
 …but in most birth cohort studies dogs
  have no effect on sensitisation to dog

• No difference
  between those
  with/without dogs
  in
  – Isle of Wight
  – PIAMA
  – COAST




                             Simpson PhD thesis 2009
           For sensitisation to any allergen

                                                    • COAST study also
 35                                                   shows less atopy in
 30                                                   dog owners at 1 year
 25                                                 • Risk of eczema
 20                                no dogs            related to genotype
                                   1 dog
 15
                                   2 or more dogs
                                                    • Effect has gone by
 10                                                   age 3 years
  5
                                                    • No evidence of an
  0                                                   increase in risk in any
           % sensitised
                                                      study

Ownby et al, JAMA 2002; Bufford et al 2008
       Question 1

How do I stop my child from
  becoming allergic to pets?
             Answer 1

•   Don’t know
•   Can become sensitised even if
    don’t live with pets
•   No evidence of hypoallergenic
    breeds
   We don’t know how to prevent
   sensitisation to pets because

• All sensitisations are not equal
• We are not all equally at risk from
  the same exposure
• Co-exposures are important
• Genes and environment do interact
• Cannot conduct Randomised
  controlled trials
   Pet ownership and asthma

• Does it matter?
Pet sensitised pet owners – what
        is the evidence?

       Mild asthma       Brittle asthma

Mite     23%                      *75%
Dog        0                      *46%
Cat        4%                     *25%
                                  *P<0.01


                     Tunnicliffe et al Eur Respir J 1999
Pet- sensitised pet owners who
 remove their pets get better
             Cat allergen levels fall slowly after
                        cat removal
              (unless you remove the carpets and soft furnishings)




Wood et al J Allergy Clin Immunol 1989
       Clinical Question 2

• I have 2 cats and 2 dogs, am
  sensitised to cats and dogs and
  have asthma (BTS step 4). How
  can I improve my asthma control?
              Answer 2

• Get rid of the pets
• Allergen levels in the home will fall
  faster if you get rid of the carpets
  I love my cats and dogs – I would
 rather get rid of the children/partner
• Evidence from field studies
  suggests
  – HEPA filters with pet in room reduce
    levels to as if pet were elsewhere in
    house
  – Washing pets works – have to do it
    twice per week
  – HEPA vacuum cleaners have little
    effect on personal exposure
       Exposure to Fel d 1 when vacuuming
        – HEPA filters make no difference




Gore, J Allergy Clin Immunol 2005
        Pet Allergen Avoidance with Pet
                     in situ
       • Three studies have addressed pet
         allergen control measures in pet-
         sensitised pet owners.
       • Two showed small improvements in
         asthma related outcomes but one did
         not
       • Cochrane-no beneficial effect of pet
         allergen control measures for allergic
         asthma in children and adults


Francis 2003,van der Heide 1999, Wood 1998, Kilburn 2003
        Clinical question 3

1. I am pregnant and have hay
   fever. My husband is allergic to
   cats. Should we get rid of my cat
   to prevent our baby from
   developing cat allergy
             Answer 3

1. Possibly, but not for the baby
        Clinical question 4

1. Can getting a dog prevent our
   children from developing
   allergies?
2. If so which type of dog?
         Answers

Don’t know
Don’t know
 Pets and asthma – what we know

• Sensitisation to domestic pets is a
  risk factor for asthma
• Can become sensitised even if
  they have never lived with pets
• Patients sensitised and exposed
  have more severe asthma
• Pet sensitised pet exposed
  asthmatics with symptoms should
  part with the pets
What is unclear about pets and
           asthma
 – How and why some people become
   sensitised to pets?
 – Is cat and dog ownership a risk factor
   for sensitisation or is it protective?
 – Is the effect of direct exposure
   dependent upon inherited risk
 – Is the effect independent of age?
 – Do cats and dogs behave in the same
   way?
   Professor W Ollier             Professor ST Holgate

   Dr R Calam                      Professor P Holt
                                   Mrs B Holt

   Dr M Thomas                     Professor S Ahlstedt
                                   Mr L Soderstrom

Professor C Bachert               Professor Iain Buchan

    Vincent Tan
    Dr John Winn             Professor Fernando Martinez
    Professor Chris Bishop



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