1. AWMF mold guideline "Medical clinical diagnostics for indoor mold exposure" - Update 2023 AWMF Register No. 161/001.
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Hurraß J, Heinzow B, Walser-Reichenbach S, Aurbach U, Becker S, Bellmann R, Bergmann KC, Cornely OA, Engelhart S, Fischer G, Gabrio T, Herr CEW, Joest M, Karagiannidis C, Klimek L, Köberle M, Kolk A, Lichtnecker H, Lob-Corzilius T, Mülleneisen N, Nowak D, Rabe U, Raulf M, Steinmann J, Steiß JO, Stemler J, Umpfenbach U, Valtanen K, Werchan B, Willinger B, and Wiesmüller GA
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None., Competing Interests: See Table 14. Figure 1Incubation period [775, 778].Figure 2Temporal relationship between sensitization and first allergic reaction [775, 778].Figure 3Latency period [775, 778]. Figure 4Annual course of the occurrence of mold spores in the outdoor air, spore concentrations as weekly values in spores/m3 air, pollen trap in Leverkusen. Source: Mülleneisen 2023, unpublished data. A volumetric spore trap based on the Hirst principle was used to determine the concentration [269] with associated microscopic analysis of the samples. The measurement method is standardized [738].Figure 5Monthly course of spore concentrations (in spores/m3 of air) in the outdoor air for several mold genera as an example for one year and one measuring station in Germany: a) Pleospora 2021 – Berlin measuring station, b) Cladosporium 2021 – Chemnitz measuring station, c) Alternaria 2021 – Berlin measuring station, d) Epicoccum 2021 – Berlin measuring station. Missing data at the Chemnitz station in the periods: February 24, 2021 to March 1, 2021 and April 1, 2021 to April 6, 2021. The figure was provided by the German Pollen Information Service Foundation (Stiftung Deutscher Polleninformationsdienst). The concentration was determined using volumetric spore traps based on the Hirst principle [269] followed by microscopic analysis of the samples. The measurement procedure is standardized [738].Risk matrix 1. Risk of infection by mold (The darker a box, the greater the possible health risk.). Risk matrix 2.Risk of sensitization/risk of allergy caused by mold (the darker the color, the greater the possible health risk). *Proof of the clinical relevance of a sensitization determined in the allergy test required! Table 2.Important sources of frequently occurring mold species and genera (examples from practical investigations). Species or genusImportant sourcesCladosporium herbarum, Alternaria alternata, Botrytis cinereaVegetation, outdoor air-associatedAspergillus versicolor complex and Scopulariopsis brevicaulisDamp plasterXerophilic Aspergillus species of the Restrictus complex (esp. A. penicillioides and A. restrictus) as well as Aspergillus glaucus/pseudoglaucus and A. montevidensis, Wallemia sebiCellulose-containing materials with only slightly increased moistureAspergillus fumigatusComposting, rotting of plant material, indicator for thermotolerant processesChaetomium spp., Trichoderma spp., Phialophora spp.Colonizer of damp wood and cellulose materials such as cardboardPenicillium speciesPerishable food, waste, organic waste and wallpaper, house dustSarocladium strictum, Parengyodontium album, Lecanicillium psalliotae and Simplicillium spp.Polystyrene floor insulation with prolonged moisture penetrationStachybotrys chartarum, Acremonium spp, Chaetomium spp.Very moist, cellulose-containing building materialsWallemia sebi, Aspergillus restrictus complexKeeping caged animals with bedding Table 3.Examples of species complexes based on molecular analyses (modified according to [297]). Complex or groupSelected speciesMolecular markers for differentiationAspergillus versicolor complexA. versicolor, A. amoenus, A. creber, A. jensenii, A. protuberus, et al.CaM, β-TubAspergillus niger complexA. niger, A. acidus, A. aculeatus, A. brasiliensis, A. tubingensis, et al.CaM, β-TubAspergillus fumigatus complexA. fumigatus, A. lentulus, A. novofumigatus, A. fumigatiaffinis, et al.CaM, β-Tub (Note: Cultivation at 37 °C; Differentiation A. lentulus)Fusarium solani complexF. solani, F. keratoplasticum, F. petroliphilum, F. lichenicola, et al.EF-1α, RPB-1 and/or RPB-2 Table 4.Evidence for the relationship between indoor moisture/mold exposure and disease (in alphabetical order), modified from [7, 39, 45, 58, 59, 74, 78, 79, 80, 101, 108,111, 116, 119, 131, 133, 162, 169, 175, 181, 182, 183, 201, 202, 204, 211, 212, 245, 263, 273, 275, 287, 289, 291, 298, 303, 316, 319, 322, 338, 363, 370, 394, 437, 442, 444, 445, 449, 450, 451, 462, 465, 466, 467, 490, 499, 501, 504, 509, 514, 520, 521, 522, 525, 526, 528, 532, 534, 537, 540, 546, 547, 552, 553, 568, 569, 596, 598, 632, 635, 642, 643, 644, 645, 652, 655, 694, 698, 717, 722, 742, 746, 754, 756, 757, 777, 783, 790, 791, 794, 797]. Causal relationship Sufficient evidence for an association1Allergic bronchopulmonary aspergillosis (ABPA) Allergic bronchopulmonary mycoses (ABPM) Allergic respiratory diseases Allergic rhinitis Allergic rhinoconjunctivitis Aspergilloma Aspergillosis Aspergillus bronchitis Asthma (manifestation, progression, exacerbation) Bronchitis (acute, chronic) Community-acquired aspergillus pneumonia Favoring respiratory infections Hypersensitivity pneumonitis (HP); extrinsic allergic alveolitis (EAA) Invasive aspergillosis Mycoses Organic dust toxic syndrome (ODTS) (workplace) Pulmonary aspergillosis (subacute, chronic) Rhinosinusitis (acute, chronic invasive or granulomatous, allergic)Limited or suspected evidence of an associationAtopic eczema / atopic dermatitis / neurodermatitis (manifestation) Chronic obstructive pulmonary disease (COPD) Mood disorders Mucous membrane irritation (MMI) Odor effects SarcoidosisInadequate or insufficient evidence for an associationAcute idiopathic pulmonary hemorrhage in children Airborne mycotoxicosis Arthritis Autoimmune diseases Cancer Chronic fatigue syndrome (CFS) Endocrinopathies Gastrointestinal effects Multiple Chemical Sensitivity (MCS) Multiple sclerosis Neuropsychological effects Neurotoxic effects Sudden infant death syndrome Renal effects Reproductive disorders Rheumatism Sick building syndrome (SBS) Teratogenicity Thyroid diseases Urticaria 1The diseases listed here can be subsumed under the term Building Related Illness (BRI), even though BRI requires that the etiology, pathology, pathophysiology, diagnosis, treatment, prevention and prognosis are clearly known [429, 663]. Table 5.Examples of typical antigens and antigen sources for hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis (EAA) (mod. after Costabel et al. 2020 [113]). AntigenAntigen sourceHP typeBacteria Thermophilic actinomycetesMoldy hay and straw Farmer’s lungSugar cane dustBagassosis Klebsiella oxytocaHumidifierHumidifier lung Mycobacteria Mycobacterium avium complexWhirlpoolsWhirlpool lung (hot tub lung) Mycobacterium immunogenumCooling lubricantsMachinist’s lungMushrooms Absidia corymbiferaMoldy hay and straw Farmer’s lung Trichosporon cutaneumInteriorsSummer-type alveolitis Penicillium roquefortiCheese production/industrial sourcesCheese washer lung Purpureocillium lilacinum, Aspergillus spp. Wind instrumentsWind instrument alveolitisAnimal proteins Feathers and excrementBirdsBird keeper lung Serum and urineRatsRat protein alveolitisPlant proteins Nut dustTiger nutsTigernut alveolitis Soy dustSoy productsSoy dust alveolitis Wood dustVarious wood dustsWoodworker’s alveolitisEnzymes PhytaseAnimal feed productionPhytase alveolitis Enzymes from Bacillus subtilisBiological cleaning agentDetergent lung Table 6.Diagnostic criteria for allergic bronchopulmonary aspergillosis. a) Diagnostic criteria for allergic bronchopulmonary aspergillosis according to Rosenberg et al. [586]:Main criteria: 1. Bronchial asthma 2. Positive immediate reaction in the skin test for Aspergillus fumigatus 3. Total IgE > 417 IU/mL 4. Positive specific IgE against Aspergillus fumigatus 5. IgG antibodies against Aspergillus fumigatus 6. Blood eosinophilia (> 1,000 Eos/µL) 7. Central bronchiectasis 8. Radiological volatile or permanent pulmonary infiltratesSecondary criteria Tough mucus plugs Positive sputum culture for Aspergillus fumigatus Late reaction in the intradermal test for Aspergillus fumigatusb) Modified ISHAM diagnostic criteria for allergic bronchopulmonary aspergillosis 2021 [616]:Combination of criteria with best sensitivity/specificity: 1. Bronchial asthma 2. Aspergillus fumigatus-specific IgE > 0.35 kU/L 3. Total IgE > 500 IU/mLand at least two of the following criteria: 1. Aspergillus fumigatus-specific IgG > 27 mgA/dL 2. Bronchiectasis in CT thorax 3. Eosinophilia in the blood count > 500/µL Table 7.Mold mycoses and their pathogens [712]. Infectious disease (invasive mycosis)Pathogen (risk group according. TRBA 460 (2016) [712]AspergillosisA. fumigatus (2)A. flavus (2)A. niger (complex) (1, 2)A. terreus (2)A. nidulans (1)MucormycosisRhizopus oryzae (2)Mucor sp. (1)Rhizomucor (1)PhaeohyphomycosesCurvularia sp. (1)Bipolaris sp. (1)Alternaria sp. (1)HyalohyphomycosesFusarium sp. (1, 2)Pseudallescheria sp.= Scedosporium sp. (2)PenicilliosesTalaromyces (formerly Penicillium) marneffei (2) Table 8.Differential diagnosis of extrinsic allergic alveolitis (EAA) and organic dust toxic syndrome (ODTS) [354]. FeaturesEAAODTSExposureVarious allergensEndotoxins, high exposureIncidence2 – 30 / 10,00010 – 100 / 10,000Latency4 – 8 hours4 – 12 hoursAuscultationEnd-expiratory rales on both sides basalNormal, possibly rattling noisesLung functionRestriction (rarely obstruction, DLCO reducedNormal (possible restriction)PrecipitinsOften specific IgGMostly negative Table 9.Immunosuppression risk groups of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) at the Robert Koch Institute [349]. Risk group 1 (moderate immunosuppression/deficiency)– Granulocytopenia < 0.5 × 109 /L; (< 500/µL) probably up to 10 days (analogous to leukopenia < 1 × 109 /L; < 1,000/µL), – Autologous stem cell transplantation up to 3 months after day 0 (day of stem cell return) – Lack of CD4-positive T helper cells < 200/µL (Caveat: age-appropriate normal values in children) – Autologous stem cell transplantation up to 3 months after intensive therapy phase Patients who have more than one characteristic of the immunosuppression/deficiency listed under risk group 1 are assigned to risk group 2.Risk group 2 (severe immunosuppression/deficiency)– Granulocytopenia < 0.5 × 109 /L (< 500/μL) for more than 10 days (analogous to leukopenia < 1× 109 /L; < 1,000/μL) – Severe aplastic anemia or macrophage activation syndrome during intensive immunosuppressive therapy – Allogeneic bone marrow or stem cell transplantation up to 6 months after completion of the intensive therapy phase (important: extent of GVHD and ongoing iatrogenic immunosuppression) – Acute inpatient treatment phase for autologous stem cell transplantation or after solid organ transplantation (until discharge)Risk group 3 (very severe immunosuppression/deficiency)– Allogeneic BMT/PBSCT in intensive therapy phase (until engraftment = regeneration of granulopoiesis) – Severe GVHD grade III or IV under intensive immunosuppression The decision to assign patients after allogeneic stem cell transplantation to group 3 is ultimately made by the treating hematologist-oncologist after reviewing all findings.GVHD = graft-versus-host-disease = graft-versus-host-reaction; BMT = mone marrow transplantation; PBSCT = peripheral blood stem cell transplantation. Table 1.Medline search on the topic of the guideline (as of 12-2014 and 6-2022). KeywordsNumber of publications found Status 12-2014 [777]Number of publications found Status 6-2022Indoor mo(u)ld or indoor dampness and human health1,9493,145Indoor mo(u)ld or indoor dampness and human health and allergy1,8753,126Indoor mo(u)ld asthma440805Indoor mo(u)ld health asthma285564Indoor mo(u)ld human health asthma494Indoor mo(u)ld allergy1,198Indoor mo(u)ld health allergy434774Indoor mo(u)ld human health allergy689Indoor mo(u)ld atopy89Indoor mo(u)ld health atopy2459Indoor mo(u)ld human health atopy55Indoor mo(u)ld arthritis8Indoor mo(u)ld health arthritis4Indoor mo(u)ld human health arthritis3Indoor mo(u)ld rheumatism5Indoor mo(u)ld health rheumatism4Indoor mo(u)ld human health rheumatism3Mo(u)ld arthritis rheumatism4662Indoor mo(u)ld arthritis rheumatism2Indoor mo(u)ld health arthritis rheumatism2Indoor mo(u)ld human health arthritis rheumatism1Indoor mo(u)ld infection750Indoor mo(u)ld health infection74435Indoor mo(u)ld human health infection357Indoor mo(u)ld irritation113Indoor mo(u)ld health irritation4295Indoor mo(u)ld human health irritation85Indoor mo(u)ld symptoms1,159Indoor mo(u)ld health symptoms449724Indoor mo(u)ld human health symptoms594Indoor mo(u)ld ergosterol50Indoor mo(u)ld health ergosterol2436Indoor mo(u)ld human health ergosterol27Indoor mo(u)ld review450Indoor mo(u)ld health review301Indoor mo(u)ld human health review160266Indoor mo(u)ld trial67Indoor mo(u)ld health trial40Indoor mo(u)ld human health trial1732Indoor mo(u)ld clinical diagnosis89194Indoor mo(u)ld health clinical diagnosis113Indoor mo(u)ld human health clinical diagnosis93Indoor mo(u)ld diagnostic / diagnostics800Indoor mo(u)ld health diagnostic / diagnostics273449Indoor mo(u)ld human health diagnostic / diagnostics353Indoor mo(u)ld prevention654Indoor mo(u)ld health prevention216433Indoor mo(u)ld human health prevention358Indoor mo(u)ld treatment650Indoor mo(u)ld health treatment229360Indoor mo(u)ld human health treatment293Indoor mo(u)ld therapy507Indoor mo(u)ld health therapy196291Indoor mo(u)ld human health therapy250Indoor mo(u)ld air filter174Indoor mo(u)ld health air filter5494Indoor mo(u)ld human health air filter55 Table 10.Stage I - IV after conjunctival provocation test (CPT) [235]. Stage IForeign body sensation, reddening of the conjunctiva, onset of itchingStage IIAs I, plus lacrimation, more intense itching, reddening of the conjunctiva tarsi of the lower eyelidStage IIIAs II, additionally reddening of the conjunctiva tarsi of the upper eyelid, severe itching, blepharospasmStage IVAs III, additionally chemosis, eyelid swelling, irresistible itching Table 11.Selection of diagnostic methods without sufficient scientific evidence or without a medical or scientific basis in environmental medicine [5, 73, 232, 283, 350, 351, 352, 353, 355, 357, 512, 535, 684]. Diagnostic methods without sufficient scientific evidenceStress tests in body mediae.g., molds in the bloodAllergological examinationse.g., serial dilution titration, cytotoxic blood tests, determination of IgG and IgA antibodies directed against molds in type I allergiesInvestigations into disorders of the immune systeme.g., lymphocyte stimulation test, determination of lymphocyte subpopulations, determination of cytokinesInvestigations of the oxidative systeme.g., determination of oxidative stressOphthalmological examinationse.g., visual contrast sensitivity Test (VCS test)Diagnostic methods without a medical or scientific basisHolistic or bioenergetic diagnostic procedurese.g., electro-acupuncture according to Voll, bioresonance procedures, pendulum, Vega test, decoder dermography, biotonometry, biotensor, Kirlian photography (plasma print procedure, energetic terminal point diagnosis), regulation thermography according to Rost, auriculodiagnostics, kinesiology, aurascopy, iris diagnostics“Clinical ecology” proceduree.g., cytotoxic blood tests, provocation and neutralization test (PN test) Table 12.Examples of treatment methods without sufficient scientific evidence or without a medical or scientific basis in environmental medicine [5, 73, 160, 384, 512, 762]. Treatment methods without sufficient scientific evidence Antifungal treatment not in line with guidelines Detoxification therapy, e.g., with cholestyramine (CSM therapy) Dietary changes Homeopathic treatments Symbiosis controlTreatment methods without a medical or scientific basis Bioresonance therapy (Moratherapy) Autologous blood and urine treatment Holistic intestinal cleansing Salt therapy Clinical ecology procedures (e.g., provocation and neutralization test (PN test)) Table 13.Cochrane EBM Review by Sauni et al. (2011) [614] on the success of remediation measures after moisture or mold damage in relation to asthma and respiratory symptoms as well as the frequency of colds in adults and children. MeasureEffect on adultsEffect on childrenHome renovation (Evidence level: moderate)Wheezing (asthma): OR 0.64 (KI: 0.55 – 0.75) Rhinitis: OR 0.57 (CI: 0.55 – 0.66) Acute treatments (mean difference): MD –0.45 (KI: –0.76 – –0.14) Table 14.The authors’ declarations of conflicts of interest and their assessment are presented below: Consultant or expert activityCollaboration in a scientific advisory boardPaid lecturing or training activitiesPaid authors or co-author-shipResearch projects / conducting clinical studiesProprietary interests (patent, copyright, share ownership)Indirect interestsTopics of the guideline affected by COI; classification of the conflict of interest (IC) with regard to relevance, consequenceDr. med. Ute AurbachNoNoNoNoNoNoNoClassification: no IC Consequence: nonePriv.-Doz. Dr. med. Sven BeckerNoYesYesNoYesNoBoard member AeDAClassification: moderate IC; consequence: no voting authorization for allergological topicsProf. Dr. med. Romuald BellmannYesYesYesNoNoNoMandate holder ÖGMMClassification: moderate IC; consequence: no eligibility for antifungal therapyProf. Dr. med. Karl-Christian BergmannYesYesYesNoNoNoMandate holder DGPClassification: moderate IC; consequence: not eligible to vote on asthma-related issuesProf. Dr. med. Oliver A. CornelyYesYesYesNoNoNoNoClassification: moderate IC; consequence: no voting rights for mycosis-related topicsProf. Dr. med. Steffen EngelhartNoNoNoNoNoNoMandate holder GHUP and DGKH, Member of the Board GHUPClassification: no IC; Consequence: noneDr. rer. nat. Guido FischerNoNoNoNoNoNoNoClassification: no IC; Consequence: noneDr. rer. nat. Thomas GabrioNoNoNoNoNoNoNoClassification: no IC; Consequence: noneDr. med. Birger HeinzowNoNoNoNoNoNoNoClassification: no IC; Consequence: noneProf. Dr. med. Caroline E.W. HerrNoNoNoNoNoNoMandate holder and President of the GHUPClassification: no IC; Consequence: noneDr. rer. nat. Julia HurraßNoNoNoNoNoNoMandate holder and board member of the GHUPClassification: no IC; Consequence: noneDr. med. Marcus JoestNoNoYesNoNoNoNoClassification: low IC; consequence: no management function (coordination/AG management)Prof. Dr. med. Christian KaragiannidisNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedClassification: not possible; consequence: not entitled to voteProf. Dr. med. Ludger KlimekNoYesYesNoYesNoMandate holder AeDAClassification: moderate IC; consequence: no voting rights for immunotherapyDr. rer. nat. Martin KöberleNoNoYesNoNoNoMandate holder DDGClassification: low IC; consequence: no management function (coordination/AG management)Dr. rer. nat. Annette KolkNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedClassification: not possible; consequence: not entitled to voteDr. med. Dipl.-Chem. Herbert LichtneckerNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedClassification: not possible; consequence: not entitled to voteDr. med. Thomas Lob-CorziliusNoNoNoNoNoNoMandate holder GPAUClassification: no IC; Consequence: noneNorbert MülleneisenNoNoNoNoNoNoMandate holder DGPClassification: no IC; Consequence: noneProf. Dr. med. Dennis NowakNoNoYesNoNoNoDGAUM and DGP elected representativesClassification: low IC; consequence: no management function (coordination/AG management)Dr. med. Uta RabeNoNoYesNoNoNoMandate holder AeDAClassification: low IC; consequence: no management function (coordination/AG management)Prof. Dr. rer. nat. Monika RaulfNoNoYesNoNoNoMandate holder DGAKI and DGAUMClassification: low IC; consequence: no management function (coordination/AG management)Prof. Dr. med. Jörg SteinmannNoNoYesNoNoNoNoClassification: low IC; consequence: no management function (coordination/AG management)Prof. Dr. med. Jens-Oliver SteißNoNoYesNoNoNoMandate holder BAPPClassification: low IC; consequence: no management function (coordination/AG management)Dr. med. Jannik StemlerNoNoYesNoNoNoNoClassification: low IC; consequence: no management function (coordination/AG management)Dr. med. Ulli UmpfenbachNoNoNoNoNoNoBoard member BAPP, WAPPA, AGAS, FAAKClassification: no IC; Consequence: noneDr. rer. nat. Kerttu ValtanenNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedClassification: not possible; consequence: not entitled to voteDr. rer. nat. Sandra Walser-ReichenbachNoNoNoNoNoNoMandate holder GHUPClassification: no IC; Consequence: noneDr. rer. medic. Barbora WerchanNoNoNoNoNoNoNoClassification: no IC; Consequence: noneProf. Dr. med. Gerhard A. WiesmüllerNoNoNoNoNoNoMandate holder and Board member GHUPClassification: no IC; Consequence: noneProf. Dr. med. Birgit WillingerNoYesYesNoNoNoMandate holder DMykGClassification: low IC; consequence: no management function (coordination/AG management), (© Dustri-Verlag Dr. K. Feistle.)
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