Standard skin prick testing and sensitization to inhalant allergens across Europe – a survey from the GA2LEN network*

Authors


  • *

     An extended version of this article is published online at http://www.GA2LEN.org and http://www.eaaci.net.

  • The authors of this paper are partners in the Global Allergy and Asthma European Network (GA2LEN)

Prof. Dr. T. Zuberbier, Department of Dermatology and Allergy, Allergy-Centre-Charité,
Charité Universitätsmedizin – Berlin,
Schumannstr. 20/21, 10117 Berlin, Germany

Abstract

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA2LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15–20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA2LEN Pan-European core SPT panel.

Mobility is increasing in Europe and allergists increasingly find themselves consulted by patients from other countries. In order to correctly diagnose inhalant allergies in these patients it is useful to know the most important inhalant allergens in the different countries of Europe as they show a difference in distribution depending on the region. Furthermore, harmonization of skin prick testing (SPT) across Europe is desirable so that findings from clinical practice as well as for clinical research are more comparable. This should be in terms of the choice of a standard panel of allergens, the source of extracts or using molecular standards and the technical procedure of testing.

Skin testing for diagnosis of inhalant allergy has been used since the 19th century and is recommended as a first-line method to detect type I hypersensitivity to inhalant allergens. Regional variations in rates of sensitization to inhalant allergens have been shown in several large European studies such as the European Community Respiratory Health Survey (ECHRS) (1) and the International Study of Asthma and Allergies in Childhood (ISAAC) (2) and other multicountry studies, e.g. for adults in Iceland/Belgium/Sweden (3), and children in New Zealand/Wales/South Africa/Sweden (4) or Poland/Italy (5), and general population surveys, e.g. in Switzerland (6) and Denmark (7).

Currently, there is no published review summarizing the data for Europe. GA2LEN, the Global Allergy and Asthma European Network, is a project selected during the Sixth Framework Programme of the European Union (EU) to overcome the fragmentation of allergy and asthma research in Europe. In this project, we have gathered the data available from the literature and added a survey to compile the data from 29 GA2LEN centres in 16 European countries.

Methods

All GA2LEN centres that work in clinical allergology submitted their standard prick test procedures. Additionally, sensitization rates were assessed by 14 centres based on the results of their patient collective. Population-based sensitization data was collected in 11 studies conducted by eight centres.

Results

Current practice of skin prick testing

All centres use a number of common standards including the use of positive and negative controls, asking the patient about medication that could interfere with the skin test and taking a 3 mm diameter cut off as the definition as a positive test. Most centres evaluate skin tests after 15–20 min. These procedures are in line with published practice guidelines (8–10), the EAACI Position Paper (11), the Nordic standards (12) and the ISAAC phase II protocol (13). Published data indicate the importance of using standardized techniques, including not re-using SPT lancets which can lead to false-positive results (14). All centres reported the use of a standard panel of allergens for the most frequent inhalant allergens (Tables 1–4; most frequently tested allergens, see Table 5) supplemented with additional suspected candidate allergens depending on the patient's history. In some centres a different standard panel is used for children.

Table 1.  Standard skin prick test allergens used at the Global Allergy and Asthma European Network (GA2LEN) centres working in clinical care (additional allergens are added according to patient history). Northern Europe
 Northern Europe
GöteborgHelsinkiOdenseOsloOslo VoksentoppenStockholm
  1. 1Different grass mixes containing Dactylis glomerata, Lolium perenne, Festuca rubra, Poe pratensis, Phleum pratense, Secale cereale, Holcus lanatus, Anthoxanthum odoratum, Arrhenatherum elatius, Agrostis stolonifera, Alopecurus pratensis, Festuca pratensis.

CatCatCatCatCatCat
DogDogDogDogDogDog
Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.
Dermatophagoides farinae Dermatophagoides farinae  Dermatophagoides farinae
Phleum pratense (timothy)Phleum pratense (timothy)Grass, mixed1Phleum pratense (timothy)Phleum pratense (timothy)Phleum pratense (timothy)
BirchBetula verrucosa (birch)BirchBirchBirchBirch
Alternaria Alternaria Alternaria alt./ A. tenuisAlternaria
ArtemisiaArtemisia vulgaris (mugwort)ArtemisiaArtemisia vulgaris (mugwort)ArtemisiaArtemisia
CladosporiumCladosporium herbarumCladosporiumCladosporium herbarumCladosporium herbarum 
      Aspergillus
  HorseHorse HorseHorse
  LatexLatex Latex 
  Cow epithelia Cow's milkCow epithelia 
  Festuca pratensis PeanutAlnus glutinosa (alder) 
    CodCorylus avellana (hazel) 
    Hen's egg whiteGolden hamster epithelia 
     Rabbit 
       
       
Number of allergens tested91111111410
ManufacturerALKALK ALKAllergopharmaALK
Table 2.  Standard skin prick test allergens used at the Global Allergy and Asthma European Network (GA2LEN) centres working in clinical care (additional allergens are added according to patient history). Central Europe
 Central Europe
AmsterdamBerlin/DermatologyBerlin/PediatricsGhent/ORLGhent/PediatricsGhent/PulmonologyKrakowLodzMunich LMU/ PediatricsMunich TUUtrechtViennaZurich
  1. 1Different grass mixes containing Dactylis glomerata, Lolium perenne, Festuca rubra, Poe pratensis, Phleum pratense, Secale cereale, Holcus lanatus, Anthoxanthum odoratum, Arrhenatherum elatius, Agrostis stolonifera, Alopecurus pratensis, Festuca pratensis.

  2. 2Tree mix II: Betula verrucosa, Quercus robur, Platanus acerifolia, Fagus silvatica; ALLERGOPHARMA.

  3. 3Mould mix: Aspergillus fumigatus, Penicillium notatum, Alternaria alternata, Mucor mucedo, Cladosporium cladosporioides; HAL.

  4. 4Tree mix I: Alnus glutinosa, Corylus avellana, Populus deltoides, Ulmus campestris, Salix caprea; ALLERGOPHARMA.

  5. 5Weed mix: Urtica dioica, Plantago lanceolata, Artemisia vulgaris, Taraxacum officinale; ALLERGOPHARMA.

  6. 6Flower mix: Aster, marguerite, dahlia, chrysanthemum, golden rod; ALLERGOPHARMA.

  7. 7Weed mix: Mugwort, plantain, rumex, nettle; HAL.

 CatCatCatCatCatCatCatCatCatCatCatCatCat
 DogDogDogDogDogDog DogDogDogDogDogDog
 Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides mixDermatophagoides pteron. Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.
  Dermatophagoides farinae Dermatophagoides farinae   Dermatophagoides farinaeDermatophagoides farinaeDermatophagoides farinaeDermatophagoides farinaeDermatophagoides farinaeDermatophagoides farinae
 Grass, mixed1Grass, mixed1Phleum pratense (timothy)Grass, mixed1Grass, mixed1Phleum pratense (timothy)Phleum pratense (timothy)Grass, mixed1Grass, mixed1Grass, mixed1Grass, mixed1Phleum pratense (timothy)Grass, mixed1
 Tree mix (hazel, birch, alder; ARTU)BirchBirchTree mix (hazel, birch, alder; ALK)Tree mix (hazel, birch, alder; ALK)BirchBirchTree mix II2BirchTree mix II2Tree mix (hazel, birch, alder; ALK)Betula alba (birch)Birch
  Alternaria   Alternaria tenuis Alternaria alternataAlternaria alternataAlternaria tenuisAlternaria tenuisAlternaria alternataAlternaria
  ArtemisiaArtemisia  ArtemisiaArtemisia    Artemisia vulgaris (mugwort)Artemisia
 Mould mix (ARTU)Cladosporium herbarum   Cladosporium herbarum   Cladosporium herbarum CladosporiumCladosporium
  Aspergillus fumigatus Mould mixture3 Aspergillus fumigatus  Aspergillus niger   Aspergillus
         HorseHorse HorseHorse
  Latex         LatexLatex
 Weed mix (ARTU)Alder Acarus siroWeed mix7HazelnutJune grassFeathersSecaleGolden hamster epithelia Guinea pigCockroach
  Beech Lepidoglyphus destructor Penicillium notatumGuinea pigAcarus siroWheat, cultivatedGuinea pig Secale cereale (rye)Secale cereale (rye)
  Corylus avellana Tyrophagus putrescentiae AlderBarley, cultivatedLepidoglyphus destructorAlderRabbit Candida albicansCandida albicans
  Oak Tree mix (ash, willow, poplar; HAL) Waybread or plantainOats, cultivatedTyrophagus putrescentiaeCorylus avellanaSheep wool Fraxinus excelsior (ash)Penicillium
  Ambrosia (ragweed) Weed mix7  Peronnial rye grassTree mix I4SalixFeathers, mixed Sambucus nigra (elder)Silk
  Ribwort    Rye, cultivatedWeed mix5Goat's feathersGoat hair Ambrosia (ragweed)Alnus glutinosa (alder)
  Urtica urens    Velvet grassFlowers6 Budgerigar feathers Plantago lanceolata (ribwort)Fraxinus excelsior (ash)
       Wheat, cultivated  Tree mix I4  Corylus avellana (hazel)
       Botrytis cinerea  Weed mix5  Ambrosia (ragweed)
       Curvularia lunata      
       Alder      
       Beech      
       Corylus avellana      
       Elm      
       Oak      
       Plantago (plane)      
       Poplar      
       Orchard      
Number of allergens tested7186126132214151871821
ManufacturerARTUALK, Alyostal (Latex), Allergopharma (Cladosporium)ALKHALHALStallergene, ALK (Aspergillus)AllergopharmaAllergopharma AllergopharmaALKHAL, ALK/Alyostal (Latex)ALK, Stallergene (grass, birch, artemisia, alder, hazel, ambrosia, secale, ash)
Table 3.  Standard skin prick test allergens used at the Global Allergy and Asthma European Network (GA2LEN) centres working in clinical care (additional allergens are added according to patient history). Southern Europe
 Southern Europe
AthensCoimbraGenuaMadridMontpellierPalermoRome 
  1. 1Different grass mixes containing Dactylis glomerata, Lolium perenne, Festuca rubra, Poe pratensis, Phleum pratense, Secale cereale, Holcus lanatus, Anthoxanthum odoratum, Arrhenatherum elatius, Agrostis stolonifera, Alopecurus pratensis, Festuca pratensis.

  2. 2Artemisia vulgaris, Heliantus annuus, Iva axillaris, Solidago virgaurea, Xantheum strummarium; LOFARMA.

  3. 3Weed mix: Artemisia, Chenopodium, Parietaria, Plantago; ALK.

  4. 4Tree mix: Platanus, Populus, Salix, Ulmus; ALK.

  5. 5Tree mix: Betula, Fraxinus, Olea, Quercus, Robinia; ALK.

CatCatCatCatCatCatCat
DogDogDogDogDogDog 
Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.
Dermatophagoides farinaeDermatophagoides farinaeDermatophagoides farinaeDermatophagoides farinaeDermatophagoides farinaeDermatophagoides farinae 
Grass, mixed1Grass, mixed1Grass, mixed1Cynodon dactylonGrass, mixed1Grass, mixed1Grass, mixed1
 Tree mix5Betula verrucosa (birch) BirchBetula alba (birch) 
AlternariaAlternaria tenuisAlternaria alternataAlternariaAlternariaAlternaria tenuisAlternaria
ArtemisiaWeed mix3 ArtemisiaArtemisiaArtemisia vulgaris (mugwort)Weed mix2
CladosporiumCladosporium herbarum CladosporiumCladosporiumCladosporium 
 AspergillusAspergillus fumigatusAspergillus fumigatusAspergillusAspergillus  
        
   Latex LatexLatex 
 Olea europeaOlea europeaOlea europeaOlea europeaOlea europeaOlea europea 
 ParietariaParietaria judaicaParietaria judaicaLoliumParietariaParietaria judaicaParietaria officinalis
 FeathersCandida albicansParietaria officinalisPhragmites c (red grass)CockroachCandida albicansAmbrosia (ragweed)
 CockroachDermatophagoides microcercasCorylus avellanaSecaleBotrytisPenicillium mix (Digitatum, Expansum, Notatum) 
 Cynodon dactylonBlatella germanica (cockroach)Cupressus semperverdisBlatella germanica (cockroach)PenicilliumCupressus sempervirens 
 FusariumAcarus siroWhite carpinus (hornbeam)Blatella orientalis (cockroach)CypressWeed mix 
 PenicilliumTilia cordata Lepidoglyphus destructorPlantago (plane)Parietaria officinalis 
 CypressPinus radiata FusariumAmbrosia (ragweed)Salsola kali 
 FraxinusTree mix4 Penicillium   
 Plantago (plane)  Cupressus arizonina   
 Poplar  Platanus hybrida   
 Chenopodium  Parietaria judaica   
    Plantago Ianceolata   
    Salsola kali   
Number of allergens tested2119152319187
ManufacturerAllergopharma/ StallergeneALKStallergene Stallergene Lofarma
Table 4.  Standard skin prick test allergens used at the Global Allergy and Asthma European Network (GA2LEN) centres working in clinical care (additional allergens are added according to patient history). UK
 UK
LondonSouthhamptonSouthhampton/Pediatrics
  1. 1Different grass mixes containing Dactylis glomerata, Lolium perenne, Festuca rubra, Poe pratensis, Phleum pratense, Secale cereale, Holcus lanatus, Anthoxanthum odoratum, Arrhenatherum elatius, Agrostis stolonifera, Alopecurus pratensis, Festuca pratensis.

  2. 2Tree mix II: Betula verrucosa, Quercus robur, Platanus acerifolia, Fagus silvatica; ALLERGOPHARMA.

  3. 3Tree mix I: Alnus glutinosa, Corylus avellana, Populus deltoides, Ulmus campestris, Salix caprea; ALLERGOPHARMA.

 CatCatCat
 DogDogDog
 Dermatophagoides pteron.Dermatophagoides pteron.Dermatophagoides pteron.
  Dermatophagoides farinae 
 Phleum pratense (timothy)Grass, mixed1Phleum pratense (timothy)
 3-trees silver birch (hazel, birch, alder)BirchBirch
 Alternaria  
 Artemisia  
 Cladosporium  
 AspergillusAspergillus fumigatus 
 HorseHorse 
    
  Rabbit 
  Feathers, mixed 
  Candida albicans 
  Tree mix I (early blossoming)3 
  Tree mix II (mid blossoming)2 
  Rape 
Number of allergens tested10145
ManufacturerALK  
Table 5.  Inhalant allergens most frequently included in skin prick testing (SPT) screening panel across all centres
 Frequency tested across all centres
Number of centres testing allergen in panel/overall number of centresPercentage centres testing allergen in panel (%)
Cat29/29100
Dog26/29 90
Dermatophagoides pteroynssinus28/29 97
Dermatophagoides farinae20/29 69
Phleum pratense (timothy)29/29100
Birch26/29 90
Alternaria20/29 69
Artemisia19/29 66
Cladosporium18/29 62
Aspergillus13/29 45
Horse10/29 34
Latex 9/29 31

Standardization of extracts

Ideally, allergen extracts should be standardized so that a given size of response should have a similar clinical relevance regardless of the specific allergen or extract used. In practice this has been extremely difficult to achieve because allergen extracts are biological mixtures containing a variety of different proteins, glycoproteins and polysaccharides. Manufacturers use in-house methods to standardize their products. This achieves a measure of consistency batch-to-batch but cannot ensure standardization between manufacturers. Clinical data from the Netherlands indicates that results obtained with different extracts do not provide comparable results (15). The importance of standardization beyond manufacturer's units lead to the development of five certified World Health Organization (WHO)-reference materials. This aspect was also emphasized in the position paper of the EAACI from 1993 (16).

In Tables 1–4 the allergen extracts used for standard SPT at the different centres are listed. An initiative to develop candidate certified reference materials consisting of purified natural or recombinant major allergens and validate existing sandwich enzyme-linked immunosorbent assay (ELISA) for the measurement of major allergens has been funded by the EU under the Fifth Framework Program. This project ‘Development of Certified Reference Materials for Allergenic Products and Validation of Methods for their Quantification CREATE (17) brings together allergen manufacturers, biotech companies, regulatory bodies, clinicians and research laboratories in order to pave the way for a successful implementation of allergen standardization based on mass units. CREATE focuses on the four main allergens birch (Bet v1), grass (Phl p1, Phl p5), olive (Ole e1) and house dust mite (Der p1, Der p2 and Der f1, Der f2) (18).

Sensitization rates – regional differences

Variation in the rates of sensitization (total rates and specific rates) in different European countries is probably an important factor for differential rates of allergic disease in various European countries. These relationships have been investigated in several multinational studies. The ECHRS (19) was a landmark study of allergic disease and asthma (20, 21). It was the first study to make broad comparisons across Europe, Turkey (22) and Albania (23) with a standardized study protocol including data on more than 12 000 subjects aged 20–44 years. Large differences in the prevalence of allergic diseases were found with high rates in English-speaking countries and low prevalence rates in the Mediterranean region and eastern Europe. The ISAAC was a large global study in children using questionnaires on prevalence of asthma and rhinoconjunctivitis (2) that included the assessment of SPT and immunoglobulin E (IgE) in a population of 3000 primary school children (24).

Approximate rates of sensitization as assessed by SPT in patients tested at 14 allergy centres from the GA2LEN network are documented in Tables 6–8. We recognize that patient populations are not representative of the general population and reflect patterns of referral and differences in local health services. In the ECHRS (Table 9), rates of sensitization to Alternaria alternata and Cladosporium herbarum were highest in the UK/Ireland and northern Europe when compared with southern Europe. In contrast, much higher rates of sensitization to olive and Parietaria judaica were observed in southern Europe (Tables 6–9) (1). House dust mite was the most frequent allergen to show positive responses in 15 of 35 centres, cat in eight, cat and mite equally in one, timothy grass pollen in eight and Cladosporium in two (25). Specific results for the ECHRS have been reported in numerous publications (3, 26–34).

Table 6.  Sensitization rates to inhalant allergens (percentage of positive skin prick test results) in patients tested at Global Allergy and Asthma European Network (GA2LEN) centres working in clinical care. Northern Europe
Patient selectionType of allergenNorthern Europe
HelsinkiOdenseOslo overall
Patients tested at centrePatients tested at centreFamilies with asthmatic children
  1. 1Grass mix –Phleum pratense, Lolium perenne, Dactylis glomerata.

  2. 2Tree mix –Betula pendula, Alnus glutinosa, Corylus avellana.

  3. 3Tree mix I –Alnus glutinosa, Corylus avellana, Populus deltoides, Ulmus campestris, Salix caprea; ALLERGOPHARMA.

  4. 4Tree mix II –Betula verrucosa, Quercus robur, Platanus acerifolia, Fagus silvatica; ALLERGOPHARMA.

  5. 5Pollen mix –Cupressus arizonina, Platanus hybrida, Olea europea, Secale, Lolium, Cynodon dactylon, Phragmites, Plantago Ianceolata, Salsola kali, mugwort, Parietaria judaica.

n 54052565424
Cat (%)Animal25.423.030.0
Dog (%)Animal28.626.025.5
Cow (%)Animal3.9  
FeathersAnimal   
Guinea pig (%)Animal   
Horse (%)Animal9.610.0 
Cynodon dactylonGrass pollen   
Festuca pratensis (meadow, %)Grass pollen24.7  
Grass mix1Grass pollen 36.0 
Phleum Pratense (timothy, %)Grass pollen24.2  
Acarus siro (%)Insect   
Cockroach (%)Insect  7.3
Dermatophagoides (%)Insect   
Dermatophagoides farinae (%)Insect 21.09.7
Dermatophagoides pteronyssinus (%)Insect6.925.012.5
Lepidoglyphus destructor (%)Insect   
Tyrophagus putrescentiae (%)Insect   
Latex (%)Latex1.010.0 
Alternaria alternata (%)Mould 4.02.6
Aspergillus (%)Mould   
Aspergillus fumigatus (%)Mould   
BotrytisMould   
Candida albicans (%)Mould   
Cladosporium (%)Mould 4.05.4
Cladosporium cladosporioides (%)Mould   
Cladosporium herbarum (%)Mould3.3  
Fusarium (%)Mould   
Mould mix (%)Mould   
Penicillium (%)Mould   
3-trees (Alder, silver birch, hazel, %)Tree pollen   
Alder (%)Tree pollen   
Betulla verucosa (%)Tree pollen30.0  
Birch Pollen (%)Tree pollen 31.0 
Corylus avellana (%)Tree pollen   
Cupressus semperverdisTree pollen   
Cypress pollenTree pollen   
Fraxinus (%)Tree pollen   
Olea europea (%)Tree pollen   
Plane treeTree pollen   
Poplar (%)Tree pollen   
Tree mix2 (%)Tree pollen   
Tree mix (willow, poplar, %)Tree pollen   
Trees I3 (%)Tree pollen   
Trees II4 (%)Tree pollen   
Waybread (%)Tree pollen   
White carpinus (%)Tree pollen   
Ambrosia (ragweed, %)Weed pollen   
Artemisia vulgaris (mugwort, %)Weed pollen15.815.08.7
Chenopodium (%)Weed pollen   
Weed mix (%)Weed pollen   
Flowers (%)Weed pollen   
Parietaria (%)Weed pollen   
Plantago (%)Weed pollen   
Pollen mix5Pollen   
Secale cereale (%)    
Title of study   GAIN
Year tested 1995–200320032002
Reference   (32)
Table 7.  Sensitization rates to inhalant allergens (percentage of positive skin prick test results) in patients tested at Global Allergy and Asthma European Network (GA2LEN) centres working in clinical care. Central Europe
Patient selectionType of allergenCentral Europe
AmsterdamBerlinGhentLodzMunich, TUVienna
Patients tested at centrePeople with suspected allergy from population sampleRhinitis patients at ORL departmentPatients tested at centrePatients tested at centrePatients tested at centre
  1. 1Grass mix –Phleum pratense, Lolium perenne, Dactylis glomerata.

  2. 2Tree mix –Betula pendula, Alnus glutinosa, Corylus avellana.

  3. 3Tree mix I –Alnus glutinosa, Corylus avellana, Populus deltoides, Ulmus campestris, Salix caprea; ALLERGOPHARMA.

  4. 4Tree mix II –Betula verrucosa, Quercus robur, Platanus acerifolia, Fagus silvatica; ALLERGOPHARMA.

  5. 5Pollen mix –Cupressus arizonina, Platanus hybrida, Olea europea, Secale, Lolium, Cynodon dactylon, Phragmites, Plantago Ianceolata, Salsola kali, mugwort, Parietaria judaica.

n 7867651622325665126 (for 5 allergens); 62 (for other allergens)
Cat (%)Animal10.019.416.012.525.428.0
Dog (%)Animal17.012.89.98.69.23.0
Cow (%)Animal      
FeathersAnimal   5.1  
Guinea pig (%)Animal  3.1  3.0
Horse (%)Animal     3.0
Cynodon dactylonGrass pollen      
Festuca pratensis (meadow, %)Grass pollen      
Grass mix1Grass pollen26.033.822.822.832.546.0
Phleum Pratense (timothy, %)Grass pollen      
Acarus siro (%)Insect  8.011.5 29.0
Cockroach (%)Insect      
Dermatophagoides (%)Insect     29.0
Dermatophagoides farinae (%)Insect  26.520.5  
Dermatophagoides pteronyssinus (%)Insect37.010.135.219.915.7 
Lepidoglyphus destructor (%)Insect  10.510.5  
Tyrophagus putrescentiae (%)Insect  10.512.9  
Latex (%)Latex 0.9   0.0
Alternaria alternata (%)Mould 1.72.57.316.411.0
Aspergillus (%)Mould      
Aspergillus fumigatus (%)Mould  1.8   
BotrytisMould      
Candida albicans (%)Mould     3.0
Cladosporium (%)Mould 1.1   2.0
Cladosporium cladosporioides (%)Mould  1.2   
Cladosporium herbarum (%)Mould      
Fusarium (%)Mould      
Mould mix (%)Mould6.3 4.3   
Penicillium (%)Mould  1.2   
3-trees (Alder, silver birch, hazel, %)Tree pollen  8.6   
Alder (%)Tree pollen  8.6   
Betulla verucosa (%)Tree pollen      
Birch Pollen (%)Tree pollen 31.57.4 29.132.0
Corylus avellana (%)Tree pollen  6.8   
Cupressus semperverdisTree pollen      
Cypress pollenTree pollen      
Fraxinus (%)Tree pollen     11.0
Olea europea (%)Tree pollen      
Plane treeTree pollen      
Poplar (%)Tree pollen      
Tree mix2 (%)Tree pollen13.0     
Tree mix (willow, poplar, %)Tree pollen  4.9   
Trees I3 (%)Tree pollen   13.5  
Trees II4 (%)Tree pollen   17.2  
Waybread (%)Tree pollen  5.6   
White carpinus (%)Tree pollen      
Ambrosia (ragweed, %)Weed pollen     11.0
Artemisia vulgaris (mugwort, %)Weed pollen 15.24.3 12.818.0
Chenopodium (%)Weed pollen      
Weed mix (%)Weed pollen1.3 8.620.1  
Flowers (%)Weed pollen   17.9  
Parietaria (%)Weed pollen    0.7 
Plantago (%)Weed pollen     6.0
Pollen mix5Pollen      
Secale cereale (%)      29.0
Title of study  PANE    
Year tested 4 years1999–20001999–2000200320032004
Reference  (35)    
Table 8.  Sensitization rates to inhalant allergens (percentage of positive skin prick test results) in patients tested at Global Allergy and Asthma European Network (GA2LEN) centres working in clinical care. Southern Europe
Patient selectionType of allergenSouthern Europe
AthensGenuaMadridMontpellierPalermo
Asthmatic children 7–9 yrs.; Children tested at centre 6–15 yrs.Children tested at centreRhinitis or asthma patientsPatients tested at centrePatients tested at centre
  1. 1Grass mix –Phleum pratense, Lolium perenne, Dactylis glomerata.

  2. 2Tree mix –Betula pendula, Alnus glutinosa, Corylus avellana.

  3. 3Tree mix I –Alnus glutinosa, Corylus avellana, Populus deltoides, Ulmus campestris, Salix caprea; ALLERGOPHARMA.

  4. 4Tree mix II –Betula verrucosa, Quercus robur, Platanus acerifolia, Fagus silvatica; ALLERGOPHARMA.

  5. 5Pollen mix –Cupressus arizonina, Platanus hybrida, Olea europea, Secale, Lolium, Cynodon dactylon, Phragmites, Plantago Ianceolata, Salsola kali, mugwort, Parietaria judaica.

n 130; 827  4042000
Cat (%)Animal30–4330.015.025.013.0
Dog (%)Animal9–19.7 14.013.011.0
Cow (%)Animal     
FeathersAnimal14–16.5    
Guinea pig (%)Animal     
Horse (%)Animal     
Cynodon dactylonGrass pollen23–27    
Festuca pratensis (meadow, %)Grass pollen     
Grass mix1Grass pollen43–4450.0  12.0
Phleum Pratense (timothy, %)Grass pollen     
Acarus siro (%)Insect     
Cockroach (%)Insect5.5 25.013.0 
Dermatophagoides (%)Insect 80.020.0  
Dermatophagoides farinae (%)Insect19–23  38.015.0
Dermatophagoides pteronyssinus (%)Insect35.8–37  43.016.0
Lepidoglyphus destructor (%)Insect     
Tyrophagus putrescentiae (%)Insect     
Latex (%)Latex 15–20 2.5 
Alternaria alternata (%)Mould19.5–20.510.014.010.7 
Aspergillus (%)Mould5.5  3.2 
Aspergillus fumigatus (%)Mould 10.0   
BotrytisMould   2.7 
Candida albicans (%)Mould     
Cladosporium (%)Mould2.5  2.7 
Cladosporium cladosporioides (%)Mould     
Cladosporium herbarum (%)Mould     
Fusarium (%)Mould6.0    
Mould mix (%)Mould     
Penicillium (%)Mould3.0  2.9 
3-trees (Alder, silver birch, hazel, %)Tree pollen     
Alder (%)Tree pollen     
Betulla verucosa (%)Tree pollen 40.0   
Birch Pollen (%)Tree pollen   8.2 
Corylus avellana (%)Tree pollen 40.0   
Cupressus semperverdisTree pollen 30.0   
Cypress pollenTree pollen   34.8 
Fraxinus (%)Tree pollen29.0    
Olea europea (%)Tree pollen33–3840.0 25.010.0
Plane treeTree pollen   15.0 
Poplar (%)Tree pollen6.0    
Tree mix2 (%)Tree pollen     
Tree mix (willow, poplar, %)Tree pollen     
Trees I3 (%)Tree pollen     
Trees II4(%)Tree pollen     
Waybread (%)Tree pollen     
White carpinus (%)Tree pollen 30.0   
Ambrosia (ragweed, %)Weed pollen   6.7 
Artemisia vulgaris (mugwort, %)Weed pollen25.0  10.4 
Chenopodium (%)Weed pollen18.0    
Weed mix (%)Weed pollen   33.0 
Flowers (%)Weed pollen     
Parietaria (%)Weed pollen25–27.580.0 9.820.0
Plantago (%)Weed pollen10.0    
Pollen mix5Pollen  66.0  
Secale cereale (%)      
Title of study  ECRHS   
Year tested 1998; 1996  20032003
Reference   (34)(48) 
Table 9.  Sensitization rates to inhalant allergens (percentage of positive skin prick test results) in patients tested at Global Allergy and Asthma European Network (GA2LEN) centres working in clinical care. ECHRS
Patient selectionType of allergenECHRS
Only asthmatics
ECRHS OverallECHRS NorthernECRHS CentralECHRS SouthernECHRS UK/IrelandECHRS Australia/NZECRHS Portland
  1. 1Grass mix –Phleum pratense, Lolium perenne, Dactylis glomerata.

  2. 2Tree mix –Betula pendula, Alnus glutinosa, Corylus avellana.

  3. 3Tree mix I –Alnus glutinosa, Corylus avellana, Populus deltoides, Ulmus campestris, Salix caprea; ALLERGOPHARMA.

  4. 4Tree mix II –Betula verrucosa, Quercus robur, Platanus acerifolia, Fagus silvatica; ALLERGOPHARMA.

  5. 5Pollen mix –Cupressus arizonina, Platanus hybrida, Olea europea, Secale, Lolium, Cynodon dactylon, Phragmites, Plantago Ianceolata, Salsola kali, mugwort, Parietaria judaica.

n        
Cat (%)Animal31.452.731.618.727.822.728.1
Dog (%)Animal       
Cow (%)Animal       
FeathersAnimal       
Guinea pig (%)Animal       
Horse (%)Animal       
Cynodon dactylonGrass pollen       
Festuca pratensis (meadow, %)Grass pollen       
Grass mix1Grass pollen       
Phleum Pratense (timothy, %)Grass pollen41.339.438.134.044.444.848.7
Acarus siro (%)Insect       
Cockroach (%)Insect       
Dermatophagoides (%)Insect       
Dermatophagoides farinae (%)Insect       
Dermatophagoides pteronyssinus (%)Insect47.723.548.234.058.167.241.0
Lepidoglyphus destructor (%)Insect       
Tyrophagus putrescentiae (%)Insect       
Latex (%)Latex       
Alternaria alternata (%)Mould11.910.213.74.717.610.528.2
Aspergillus (%)Mould       
Aspergillus fumigatusMould       
BotrytisMould       
Candida albicans (%)Mould       
Cladosporium (%)Mould       
Cladosporium cladosporioides (%)Mould       
Cladosporium herbarum (%)Mould5.89.94.30.76.84.510.3
Fusarium (%)Mould       
Mould mix (%)Mould       
Penicillium (%)Mould       
3-trees (Alder, silver birch, hazel, %)Tree pollen       
Alder (%)Tree pollen       
Betulla verucosa (%)Tree pollen       
Birch Pollen (%)Tree pollen19.439.818.010.08.813.133.3
Corylus avellana (%)Tree pollen       
Cupressus semperverdisTree pollen       
Cypress pollenTree pollen       
Fraxinus (%)Tree pollen       
Olea europea (%)Tree pollen       
Plane treeTree pollen       
Poplar (%)Tree pollen       
Tree mix2 (%)Tree pollen       
Tree mix (willow, poplar, %)Tree pollen       
Trees I3 (%)Tree pollen       
Trees II4 (%)Tree pollen       
Waybread (%)Tree pollen       
White carpinus (%)Tree pollen       
Ambrosia (ragweed, %)Weed pollen2.63.83.62.72.90.37.7
Artemisia vulgaris (mugwort, %)Weed pollen       
Chenopodium (%)Weed pollen       
Weed mix (%)Weed pollen       
Flowers (%)Weed pollen       
Parietaria (%)Weed pollen       
Plantago (%)Weed pollen       
Pollen mix5Pollen       
Secale cereale (%)        
Title of study        
Year tested        
Reference (1)      

Population-based studies with assessment of type I sensitizations have been conducted in Germany (35), Denmark (7), with a follow-up study 8 years later (36), in Switzerland (6), Finland (37), Italy and in the UK (37). Limited to children or adolescents additional data exists for the Netherlands (23, 39), Denmark (40), Finland (41), Germany (42), UK (43) and Poland/Italy (5). An overview of selected studies including type I sensitization as assessed by SPT is given in Table 10, and the sensitization rates found in these studies with general populations are listed in Table 11.

Table 10.  Overview of the studies published with results on standard skin prick testing
CountryStudy populationSubgroupAge group (years old)Number of subjectsYear of studySPT results statedAuthorYear published
FranceChildren and adultsAsthmatic families0 to >801847Not statedNo specific SPT results statedKauffmann et al.1999
NorwayChildren and adults100 Norwegian families of 7–35-year-old sibling pairs with asthma>7 years4241998–99xLodrup Carlsen et al.2002
SpainAdultsPatients with rhinitis and/or asthma6–68171Not statedxSastre et al.1996
SwedenAdultsAsthmatics sensitized to cat or dog18–60129Not statedxPlaschke et al.1999
DenmarkAdolescents and adultsGeneral population15–691112 (635 symptomatic; 477 control)1990–91No specific SPT results statedLinneberg et al.2001
DenmarkAdolescents and adultsGeneral population15–41312; 4821990; 1998(x) summarizedLinneberg et al.2000
GermanyChildren and adultsGeneral population0 to >808141999–2000xZuberbier et al.2004
SwitzerlandAdultsGeneral population18–6085371991–93xWuthrich2001
UKAdultsGeneral population30–651359; 741974; 1988 Sibbald et al.1990
DenmarkAdolescentsUnselected 8th grade school children14–1615011996–97xMortz et al.2003
GermanyChildrenUnselected school children9–111303; 16421991–92; 1995–96xvon Mutius et al.1998
The NetherlandsChildrenUnselected school children7–12450Not statedxvan Amsterdam et al.2003
The NetherlandsChildrenUnselected school children7–123000Not stated(x) summarizedAnyo et al.2002
Poland, ItalyChildrenUnselected school children9 years3361998–99xRonchetti et al.2003
UKChildrenBirth cohort4 years9811989–90xArshad et al.2001
GermanyChildrenUnselected pre-school children5–712731991xSchäfer et al.1996
Table 11.  Sensitization rates to inhalant allergens in population-based studies (percentage of positive skin prick test results assessed in different population samples)
Population sampleType of allergenNorthCentralUKSouthern
FinlandFinlandOslo, NorwayThe NetherlandsPolandMunich, Germany (1991)Munich, Germany (1991–1992)Munich, Germany (1995–1996)Zurich, SwitzerlandRome, ItalyRome, Italy
General population (25–54 years)Adolescents, (15–17 years; M/F)Control subjects with no asthma, no rhinitisSchool children (7–12 years)School children (9 years)Children (5–7 years)Children (9–11 years)Children (9–11 years)General population (18–60 years)Birth cohort (4 years)School children (9 years)General population (10–50 years)
  1. 1Grass mix –Phleum pratense, Llolium perenne, Dactylis glomerata.

  2. 2Tree mix –Betula verrucosa, Alnus glutinosa, Corylus avellana.

  3. M, male; F, female.

n 79070810445013810951303164285379811984936
Cat (%)Animal 12.718–36/11–28 14.48.8  3.6   9.8   3.3   3.1   3.8  5.8  5.6   6.3
Dog (%)Animal 12.97–19/3–10 11.54.1     2.8   2.6   2.8  2.7  
Horse (%)Animal  2.923/18          
Cow (%)Animal  2.6           
Grass mix1 (%)Grass pollen 23/14 17.314.4  8.7  12.8   9.1  11.5  12.7  7.8 11.6  27.5
Timothy grass (%)Grass pollen 10.323/13          
Cockroach (%)Insect  7.2   7.7         
Dermatophagoides (%)Insect        7.4   4.6   8.1   8.9 11.9   25.2
Dermatophagoides farinae (%)Insect 15–21/13–18  7.714.1  3.6      10.6 
Dermatophagoides pteronyssinus (%)Insect  7.0   4.817.2  9.4      16.7 
LatexLatex            
Alternaria alternata (%)Mould  2.2   1.91.9       1.1  5.1    3.40
Alternaria tenuis (%)Mould      0.7       1.5 
Cladosporium (%)Mould  3.3   1.9       <1  2.2  
Birch Pollen (%)Tree pollen 12.315/11      5.9   8.4  14.2   7.9   
Corylus avellana (%)Tree pollen         3.8   6.7    
Alnus sp. (alder) (%)Tree pollen 14/9          
Tree mix2 (%)Tree pollen   3.8 2.2       4.0 
Olea europea (%)Tree pollen             13.50
Ambrosia (ragweed) (%)Weed pollen              2.80
Parietaria (%)Weed pollen             15.60
Artemisia vulgaris (mugwort) (%)Weed pollen  7.819/11 12.5           5.40
Chrysanthemum leucanthemum (%)Weed pollen 12/7          
Title of study   GAIN     Sapaldia   
Year tested 199819782002Not stated 1998–2000 1991–19921995–19961991–19931989–19901998–19992003–2004
Reference (37)(41)(32)(39)(5)(49)(42)(42)(6)(43)(5)S. Bonini

Discussion

In recent years, mobility for work has increased dramatically within Europe. Moreover, leisure travel has become much more common. Climatic and agricultural changes are also influencing sensitization to inhalant allergens, for example, the botanical range of Artemisia and Parietaria have expanded in recent years and new crops, including olive trees, are now grown much more frequently in central Europe. These changes are superimposed on other trends in the prevalence of allergy and asthma (44, 45). A critical appraisal of studies investigating these trends with objective measurements has been undertaken in a review by Wieringa et al. (44, 45).

There is general agreement across the different centres participating in this study on the common ‘core’ panel of airborne allergens that should be used for investigating patients with asthma and rhinitis. There would be clear advantages in further harmonizing this panel across different centres, both within each country and between countries. Both technical factors (skin prick technique, timing of assessment, etc.) and the source of the allergen extracts should ideally be harmonized to make results truly comparable. Further improvements could be achieved by moving to the use of recombinant allergens as opposed to the current biological preparations. There may be some advantage in increasing the scope of the core panel to cover allergens that are found commonly in other parts of Europe. This would help allergists to recognize sensitization to allergens from different regions that may be encountered by patients travelling elsewhere on holiday or business and would also allow us to recognize relevant sensitization in patients who have migrated.

Conclusion

Especially with increasing mobility across Europe it is important to keep in mind that sensitization to inhalant allergens differ regionally. The sensitization frequencies in the different countries that are compiled in this article may serve as a point of reference. Several EU initiatives (46) are now supporting the harmonization of allergen research, clinical practice and training across Europe (47). The development of a standardized Pan-European inhalant allergen panel is a desirable objective and would help to generate more relevant data for future clinical practice and clinical research. The use of a common core panel, does not preclude the use of extended, centre-specific, panels or specific allergens for special patients. A standard SPT panel for Europe is proposed by GA2LEN (see Table 12).

Table 12.  Pan-European standard prick test panel**
  1. *may be tested as single allergens

  2. **may be supplemented with other suspected candidate allergens

Cat
Dog
Dermatophagoides pteronyssinus
Dermatophagoides farinae
Blatella
Tree mix Northern (Birch, hazel, alder)*
Olive
Cypress
Plane
Grass mix
Artemisia
Ambrosia
Parietaria
Alternaria
Cladosporium
Aspergillus

Acknowledgments

Further partners who have contributed towards this manuscript are Ana Todo-Bom, Coimbra; Bert Brunekreef, Utrecht; Peter Burney and Stephen Durham, London; Roelinde Middelveld, Stockholm; Erika von Mutius, Munich; Bodo Niggemann and Martina Lütticke, Berlin; Sabina Rak, Gothenburg; Andrew Szczeklik, Krakow. We also thank Cindy Mettepenningen and the GA2LEN office for continuous support.

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