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Bei der Behandlung des Themas 'Familie' steht die Kinder- und Jugendpsychiatrie in enger Verbindung zu anderen ärztlichen Gebieten (Pädiatrie, Psychiatrie, Neurologie), dem Erziehungs- und und Bildungsbereich und der Jugendhilfe. Hinter diesem professionellen, mehr oder weniger gemeinsamen Ganzen steht aber noch jedes Einzelnen Beziehung zur Familie, vor allem zu seiner Herkunftsfamilie, die nun mal das Bild von Selbst und Familie prägt und auch das professionelle Bild von Familie bestimmt. Die Annahme der vollständigen Familie impliziert ein Idealbild, das den Einzelnen von uns in die berufliche und persönliche Schwierigkeit bringt, im alltäglichen Erleben mit ganz anderen Bildern konfrontiert zu sein: mit zwar noch vollständigen, aber heillos zerstrittenen, mit kranken und in zunehmender Zahl mit unvollständigen Familien. In dieser Hinsicht haben Kinder- und Jugendpsychiater ständig eine besonders große Kluft zwischen Überzeugungen, Wünschen und Hoffnungen auf der einen und nur mit Kompromißbereitschaft annehmbaren Realitäten auf der anderen Seite zu überbrücken.

German recommendations for the diagnosis of hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis (EAA), were last published in 2007 [1]. The current S2k Guideline for the Diagnosis and Treatment of Hypersensitivity Pneumonitis (HP) replaces these diagnostic recommendations. They were supplemented by the aspect of chronic, and in particular of the chronic fibrotic phenotype of HP, and also, as first HP guideline, include treatment recommendations. Based on current scientific evidence and on expert opinion 12 consensus recommendations were developed. They include important statements summarizing the diagnostic process, the treatment indication and therapeutic strategies for patients with HP. Particular emphasis was placed on the different clinical courses (acute and chronic) and their characteristics (inflammatory and/or fibrotic pattern), which present differential diagnostic challenges and ultimately result in different treatment approaches. In addition to general information (diagnosis, classification, clinical disease course, epidemiology, pathogenesis, risk factors, prognosis and special aspects associated with occupational disease), the guideline will present the various clinical disease entities of HP, some in detail, others in tabular form. A major focus is on the various diagnostic steps and the different treatment approaches. The background information serves to provide a deeper understanding and inform the implementation of the recommendations. In particular, other current international guidelines for the diagnosis of HP as well as German guidelines for the diagnosis of Interstitial lung diseases (ILDs) (Leitlinien zur Diagnostik interstitieller Lungenerkrankungen) in general and for the pharmacotherapy of fibrotic ILDs were integrated and considered in this guideline [2-6]., (The Author(s). Published by S. Karger AG, Basel.)

Bacterial cell division and plant chloroplast division require selfassembling Filamentous temperature-sensitive Z (FtsZ) proteins. FtsZ proteins are GTPases sharing structural and biochemical similarities with eukaryotic tubulin. In the moss Physcomitrella, the morphology of the FtsZ polymer networks varies between the different FtsZ isoforms. The underlying mechanism and foundation of the distinct networks is unknown. Here, we investigated the interaction of Physcomitrella FtsZ2-1 with FtsZ1 isoforms via co-immunoprecipitation and mass spectrometry, and found protein-protein interaction in vivo. We tagged FtsZ1-2 and FtsZ2-1 with different fluorophores and expressed both in E. coli, which led to the formation of defined structures within the cells and to an influence on bacterial cell division and morphology. Furthermore, we have optimized the purification protocols for FtsZ1-2 and FtsZ2-1 expressed in E. coli and characterized their GTPase activity and polymerization in vitro. Both FtsZ isoforms showed GTPase activity. Stoichiometric mixing of both proteins led to a significantly increased GTPase activity, indicating a synergistic interaction between them. In light scattering assays, we observed GTP-dependent assembly of FtsZ1-2 and of FtsZ2-1 in a protein concentration dependent manner. Stoichiometric mixing of both proteins resulted in significantly faster polymerization, again indicating a synergistic interaction between them. Under the same conditions used for GTPase and light scattering assays both FtsZ isoforms formed filaments in a GTP-dependent manner as visualized by transmission electron microscopy (TEM). Taken together, our results reveal that Physcomitrella FtsZ1-2 and FtsZ2-1 are functionally different, can synergistically interact in vivo and in vitro, and differ in their properties from FtsZ proteins from bacteria, archaea and vascular plants., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) in sensitized individuals caused by a large variety of inhaled antigens. The clinical form of acute HP is often misdiagnosed, while the chronic form, especially the chronic fibrotic HP, is difficult to differentiate from other fibrotic ILDs. The present guideline for the diagnosis and treatment of HP replaces the former German recommendations for the diagnosis of HP from 2007 and is amended explicitly by the issue of the chronic fibrotic form, as well as by treatment recommendations for the first time. The evidence was discussed by a multidisciplinary committee of experts. Then, recommendations were formulated for twelve questions on important issues of diagnosis and treatment strategies. Recently published national and international guidelines for ILDs and HP were considered. Detailed background information on HP is useful for a deeper insight into HP and the handling of the guideline., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer 020-036., (Thieme. All rights reserved.)

This article is an abridged version of the updated AWMF mould guideline "Medical clinical diagnostics in case of indoor mould exposure - Update 2023", presented in July 2023 by the German Society of Hygiene, Environmental Medicine and Preventive Medicine (Gesellschaft für Hygiene, Umweltmedizin und Präventivmedizin, GHUP), in collaboration with German and Austrian scientific medical societies, and experts. Indoor mould growth is a potential health risk, even if a quantitative and/or causal relationship between the occurrence of individual mould species and health problems has yet to be established. There is no evidence for a causal relationship between moisture/mould damage and human diseases, mainly because of the ubiquitous presence of fungi and hitherto inadequate diagnostic methods. Sufficient evidence for an association between moisture/mould damage and the following health effects has been established for: allergic respiratory diseases, allergic rhinitis, allergic rhino-conjunctivitis, allergic bronchopulmonary aspergillosis (ABPA), other allergic bronchopulmonary mycosis (ABPM), aspergilloma, Aspergillus bronchitis, asthma (manifestation, progression, exacerbation), bronchitis (acute, chronic), community-acquired Aspergillus pneumonia, hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis (EEA)), invasive Aspergillosis, mycoses, organic dust toxic syndrome (ODTS) [workplace exposure], promotion of respiratory infections, pulmonary aspergillosis (subacute, chronic), and rhinosinusitis (acute, chronically invasive, or granulomatous, allergic). In this context the sensitizing potential of moulds is obviously low compared to other environmental allergens. Recent studies show a comparatively low sensitization prevalence of 3-22,5 % in the general population across Europe. Limited or suspected evidence for an association exist with respect to atopic eczema (atopic dermatitis, neurodermatitis; manifestation), chronic obstructive pulmonary disease (COPD), mood disorders, mucous membrane irritation (MMI), odor effects, and sarcoidosis. (iv) Inadequate or insufficient evidence for an association exist for acute idiopathic pulmonary hemorrhage in infants, airborne transmitted mycotoxicosis, arthritis, autoimmune diseases, cancer, chronic fatigue syndrome (CFS), endocrinopathies, gastrointestinal effects, multiple chemical sensitivity (MCS), multiple sclerosis, neuropsychological effects, neurotoxic effects, renal effects, reproductive disorders, rheumatism, sick building syndrome (SBS), sudden infant death syndrome, teratogenicity, thyroid diseases, and urticaria.The risk of infection posed by moulds regularly occurring indoors is low for healthy persons; most species are in risk group 1 and a few in risk group 2 ( Aspergillus fumigatus , A. flavus ) of the German Biological Agents Act (Biostoffverordnung). Only moulds that are potentially able to form toxins can be triggers of toxic reactions. Whether or not toxin formation occurs in individual cases is determined by environmental and growth conditions, water activity, temperature and above all the growth substrates.In case of indoor moisture/mould damage, everyone can be affected by odor effects and/or mood disorders.However, this is not an acute health hazard. Predisposing factors for odor effects can include genetic and hormonal influences, imprinting, context and adaptation effects. Predisposing factors for mood disorders may include environmental concerns, anxiety, condition, and attribution, as well as various diseases. Risk groups to be protected particularly regarding infection risk are immunocompromised persons according to the classification of the German Commission for Hospital Hygiene and Infection Prevention (Kommission für Krankenhaushygiene und Infektionsprävention, KRINKO) at the Robert Koch-Institute (RKI), persons suffering from severe influenza, persons suffering from severe COVID-19, and persons with cystic fibrosis (mucoviscidosis); with regard to allergic risk, persons with cystic fibrosis (mucoviscidosis) and patients with bronchial asthma must be protected. The rational diagnostics include the medical history, physical examination, and conventional allergy diagnostics including provocation tests if necessary; sometimes cellular test systems are indicated. In the case of mould infections, the reader is referred to the specific guidelines. Regarding mycotoxins, there are currently no useful and validated test procedures for clinical diagnostics. From a preventive medical point of view, it is important that indoor mould infestation in relevant magnitudes cannot be tolerated for precautionary reasons.For evaluation of mould damage in the indoor environment and appropriate remedial procedures, the reader is referred to the mould guideline issued by the German Federal Environment Agency (Umweltbundesamt, UBA)., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer 161/001., (Thieme. All rights reserved.)

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.)

Background: According to self-reported frequencies, every fifth or sixth dwelling in Germany is affected by dampness and/or mold. This carries a potential risk to health., Methods: This review is based on pertinent publications retrieved by a selective literature search and inquiry in the GENESIS database, on the AWMF guideline on the medical clinical diagnosis of indoor mold exposure, as updated in 2023, and on the relevant contents of other current guidelines. Based on this research, we present an algorithm for the evaluation of health problems that may be due to mold in indoor environments., Results: A rational diagnostic work-up begins with history-taking and physical examination, with attention to risk factors-above all, immune compromise and atopy. If there is evidence of atopy, targeted allergy diagnostics should be performed, consisting of a skin prick test and/or measurement of specific IgE antibodies, supplemented whenever indicated by provocative testing and cellular test systems. If the patient's immune response is compromised, the immediate cessation of mold exposure has absolute priority. Any suspected invasive fungal infection should be evaluated with radiological, microbiological, serological, and immunological testing. Indoor measurements of mold fungi, microbial volatile organic compounds (MVOC), and/or mycotoxins are generally not indicated as part of the medical evaluation; nor are blood or urine tests for particular mold components or metabolites., Conclusion: Mold in indoor environments should be dealt with by rapid exposure elimination for patients at risk, the rational diagnostic evaluation of any symptoms and signs of disease, and patient education about the possibilities and limitations of diagnostic testing and the generally limited utility of measurements in the affected interior spaces.

Background: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics., Methods: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively., Results: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL -1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus -IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response., Conclusion: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research., Competing Interests: Conflict of interest: R. Agarwal has received grants from Cipla Pharmaceuticals, India for conducting research in ABPA. D.W. Denning and family hold founder shares in F2G Ltd, a University of Manchester spin-out antifungal discovery company, and share options in TFF Pharma. He acts or has recently acted as a consultant to Pulmatrix, Pulmocide, Biosergen, TFF Pharmaceuticals, Rostra Therapeutics, Mucpharma PTY and Lifemine Therapeutics. In the last 3 years, he has been paid for talks on behalf of Mundipharma, Bio-Rad, Basilea, Gilead, Avir and Pfizer. He has been involved in multiple guideline groups, primarily focused on diagnostics and aspergillosis. D. Armstrong-James holds share options in Pulmocide Ltd. K. Asano is partially supported by a research grant on allergic disease and immunology from the Japan Agency for Medical Research and Development under grant number 22ek0410097. S.H. Chotirmall has served on advisory boards for CSL Behring, Pneumagen Ltd and Boehringer Ingelheim, on data monitoring boards for Inovio Pharmaceuticals and Imam Abdulrahman Bin Faisal University, and has received personal fees from AstraZeneca and Chiesi Farmaceutici, all unrelated to this work. H.J.F. Salzer has received honoraria for lectures or consulting fees from Ismed, GlaxoSmithKline, AstraZeneca, Advanz Pharma, MSD and Chiesi, all unrelated to this work. J.D. Chalmers has received research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed and Trudell, and received consultancy or speaker fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer, Trudell and Zambon. C. Godet has received speaker fees and travel support from Pfizer and MSD, fees for board memberships from SOS Oxygène and Pulmatrix, and grant support from Ohre Pharma, Pfizer, MSD, SOS Oxygène, ISIS Medical, LVL Médical, Oxyvie, Vivisol, Elivie, CF Santé, Boehringer, Sandoz and AstraZeneca. M. Joest has received honoraria for lectures or grants from ALK-Abelló, AstraZeneca, Bencard, Berlin-Chemie, Boehringer Ingelheim, GlaxoSmithKline and HAL Allergy, all unrelated to this work. P. Nair reports grants and personal fees from AstraZeneca, Teva and Sanofi, personal fees from Equillium, Arrowhead Pharma and GlaxoSmithKline, and grants from Foresee and Cyclomedica, outside the submitted work. C.G. Baxter serves on strategic advisory board for Nob Hill Therapeutics Ltd. W.J. Calhoun is a member of the scientific advisory board of Pulmatrix, and that work is unrelated to this publication. O.A. Cornely reports grants from Cidara, F2G, Gilead, MSD, Mundipharma, Pfizer and Scynexis, consulting fees from AiCuris, Basilea, Cidara, Gilead, IQVIA, Matinas, Pfizer, PSI, Pulmocide and Scynexis, honoraria for lectures from Al-Jazeera, Gilead, Knight, MSD, Pfizer and Shionogi, and payment for expert testimony from Cidara. J.A. Douglass has received honoraria for educational presentations from AstraZeneca, GlaxoSmithKline, Novartis and CSL, has served on advisory boards for Sanofi-Aventis, Novartis, GlaxoSmithKline, AstraZeneca, Immunosis and CSL, and has undertaken contracted or investigator-initiated research on behalf of GlaxoSmithKline, Novartis, Immunosis, AstraZeneca, Sanofi-Aventis, Grifols, CSL, BioCryst and Equillium. R. Moss reports consulting fees from the Cystic Fibrosis Foundation, Astellas Pharma Inc., Nob Hill Therapeutics Inc., Pulmatrix, Mayne Pharma, Zambon Company SpA, Aridis Pharmaceuticals Inc., Regeneron Pharmaceuticals Inc. and 4D Molecular Therapeutics, royalties from UpToDate, Inc., and is a member of the board of directors for the Cystic Fibrosis Research Institute. D. Seidel received speaker fees from Pfizer, outside of the submitted work. R. Sprute has received speaker fees from Hikma and Pfizer, and travel support from Pfizer, all outside of the submitted work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Background: Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with different disease trajectories. Progression (PF-ILD) occurs in up to 50% of patients and is associated with increased mortality., Methods: The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for disease trajectories in different ILD. The course of disease was classified as significant (absolute forced vital capacity FVC decline > 10%) or moderate progression (FVC decline 5-10%), stable disease (FVC decline or increase < 5%) or improvement (FVC increase ≥ 5%) during time in registry. A second definition for PF-ILD included absolute decline in FVC % predicted ≥ 10% within 24 months or ≥ 1 respiratory-related hospitalisation. Risk factors for progression were determined by Cox proportional-hazard models and by logistic regression with forward selection. Kaplan-Meier curves were utilised to estimate survival time and time to progression., Results: Within the EXCITING-ILD registry 28.5% of the patients died (n = 171), mainly due to ILD (n = 71, 41.5%). Median survival time from date of diagnosis on was 15.5 years (range 0.1 to 34.4 years). From 601 included patients, progression was detected in 50.6% of the patients (n = 304) with shortest median time to progression in idiopathic NSIP (iNSIP; median 14.6 months) and idiopathic pulmonary fibrosis (IPF; median 18.9 months). Reasons for the determination as PF-ILD were mainly deterioration in lung function (PFT; 57.8%) and respiratory hospitalisations (40.6%). In multivariate analyses reduced baseline FVC together with age were significant predictors for progression (OR = 1.00, p < 0.001). Higher GAP indices were a significant risk factor for a shorter survival time (GAP stage III vs. I HR = 9.06, p < 0.001). A significant shorter survival time was found in IPF compared to sarcoidosis (HR = 0.04, p < 0.001), CTD-ILD (HR = 0.33, p < 0.001), and HP (HR = 0.30, p < 0.001). Patients with at least one reported ILD exacerbation as a reason for hospitalisation had a median survival time of 7.3 years (range 0.1 to 34.4 years) compared to 19.6 years (range 0.3 to 19.6 years) in patients without exacerbations (HR = 0.39, p < 0.001)., Conclusion: Disease progression is common in all ILD and associated with increased mortality. Most important risk factors for progression are impaired baseline forced vital capacity and higher age, as well as acute exacerbations and respiratory hospitalisations for mortality. Early detection of progression remains challenging, further clinical criteria in addition to PFT might be helpful., (© 2024. The Author(s).)

Allergic bronchopulmonary aspergillosis (ABPA) is a regular occurrence in everyday pneumology. ABPA should be considered in patients with severe asthma, in mould allergic patients with very high serum IgE levels and in patients with cystic fibrosis. The aim should be to make the diagnosis as early as possible in the course of the disease to avoid late complications such as bronchiectasis and fibrotic lung remodelling. Symptoms are highly variable and rather non-specific, overlapping with those of the underlying primary disease. However, clearly defined diagnostic criteria exist, so that the diagnosis can be made relatively easily if one thinks of it. In therapy, systemic steroids and antifungals (mainly azoles) play the leading role. However, biologics have been gaining in importance in recent years, especially in cases of insufficient therapy response or occurrence of side effects to standard therapies, as well as an alternative in permanently steroid-dependent patients., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: ja, von einem/den Sponsor(en) dieser Fortbildungseinheit; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einem/den Sponsor(en) dieser Fortbildungseinheit; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: ja, von einem/den Sponsor(en) dieser Fortbildungseinheit; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein Erklärung zu nichtfinanziellen Interessen Joest: Mitgliedschaft DGP, ERS, AeDA, DGAKI, EAACI, BDP, WDGP. Kütting: Mitgliedschaft DRG, ESR, DEGIR, ESIR, RSNA, ESTI, SCMR. Skowasch: Mitgliedschaft DGP, ERS, DGU, ESC., (Thieme. All rights reserved.)

Background: Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with more than 200 entities and relevant differences in disease course and prognosis. Little data is available on hospitalisation patterns in ILD., Methods: The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for hospitalisations. Reasons for hospitalisation were classified as all cause, ILD-related and respiratory hospitalisations, and patients were analysed for frequency of hospitalisations, time to first non-elective hospitalisation, mortality and progression-free survival. Additionally, the risk for hospitalisation according to GAP index and ILD subtype was calculated by Cox proportional-hazard models as well as influencing factors on prediction of hospitalisation by logistic regression with forward selection., Results: In total, 601 patients were included. 1210 hospitalisations were recorded during the 6 months prior to registry inclusion until the last study visit. 800 (66.1%) were ILD-related, 59.3% of admissions were registered in the first year after inclusion. Mortality was associated with all cause, ILD-related and respiratory-related hospitalisation. Risk factors for hospitalisation were advanced disease (GAP Index stages II and III) and CTD (connective tissue disease)-ILDs. All cause hospitalisations were associated with pulmonary hypertension (OR 2.53, p = 0.005). ILD-related hospitalisations were associated with unclassifiable ILD and concomitant emphysema (OR = 2.133, p = 0.001) as well as with other granulomatous ILDs and a positive smoking status (OR = 3.082, p = 0.005)., Conclusion: Our results represent a crucial contribution in understanding predisposing factors for hospitalisation in ILD and its major impact on mortality. Further studies to characterize the most vulnerable patient group as well as approaches to prevent hospitalisations are warranted., (© 2023. The Author(s).)

Cellular senescence is an irreversible growth arrest with a dynamic secretome, termed the senescence-associated secretory phenotype (SASP). Senescence is a cell-intrinsic barrier for reprogramming, whereas the SASP facilitates cell fate conversion in non-senescent cells. However, the mechanisms by which reprogramming-induced senescence regulates cell plasticity are not well understood. Here, we investigate how the heterogeneity of paracrine senescence impacts reprogramming. We show that senescence promotes in vitro reprogramming in a stress-dependent manner. Unbiased proteomics identifies a catalog of SASP factors involved in the cell fate conversion. Amphiregulin (AREG), frequently secreted by senescent cells, promotes in vitro reprogramming by accelerating proliferation and the mesenchymal-epithelial transition via EGFR signaling. AREG treatment diminishes the negative effect of donor age on reprogramming. Finally, AREG enhances in vivo reprogramming in skeletal muscle. Hence, various SASP factors can facilitate cellular plasticity to promote reprogramming and tissue repair., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

In the workup of a 55-year-old atopic patient with cough and viscous secretions, we diagnosed an allergic bronchopulmonary aspergillosis (ABPA) on the basis of common diagnostic criteria for adult asthma patients (Rosenberg-Patterson and ISHAM), supported by the use of IgE antibodies against the Aspergillus components Asp f 2, f 4, and f 6. Initial treatment with prednisolone and itraconazole led to remission. In the long-term follow-up, there were few relapses until 2015, which responded well to standard treatment with oral steroids, and since 2016 the patient is in stable remission. The case highlights the valuable contribution of Aspergillus IgE measurements, including the specific IgEs against the components Asp f 1, f 2, f 4, and f 6 in the diagnosis of ABPA., (© Dustri-Verlag Dr. K. Feistle.)

Here we present a 79-year old man with chronic hypersensitivity pneumonitis probably caused by fungal contamination of a bagpipe. Several samples were taken from the patient's bagpipe. Four potential fungal antigens ( Exophiala phaeomuriformis, Kwoniella europaea, Pyrenochaeta unguis-hominis and Aureobasidium melanogenum ) as potential trigger of hypersensitivity pneumonitis were identified. A serum ELISA test with Exophiala phaeomuriformis indicated reactivity. Cessation of playing the bagpipe and application of glucocorticoids lead to an improvement of the patient's symptoms.

Cellular senescence has been suggested to facilitate tissue regeneration via promoting cellular plasticity. Here, we describe multiple systems, both in vitro and in vivo, to detect senescence in the context of cellular reprogramming.

In vivo reprogramming is a promising approach for tissue regeneration in response to injury. Several examples of in vivo reprogramming have been reported in a variety of lineages, but some including skeletal muscle have so far proven refractory. Here, we show that acute and chronic injury enables transcription-factor-mediated reprogramming in skeletal muscle. Lineage tracing indicates that this response frequently originates from Pax7+ muscle stem cells. Injury is associated with accumulation of senescent cells, and advanced aging or local irradiation further enhanced in vivo reprogramming, while selective elimination of senescent cells reduced reprogramming efficiency. The effect of senescence appears to be, at least in part, due to the release of interleukin 6 (IL-6), suggesting a potential link with the senescence-associated secretory phenotype. Collectively, our findings highlight a beneficial paracrine effect of injury-induced senescence on cellular plasticity, which will be important for devising strategies for reprogramming-based tissue repair., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The generation of induced pluripotent stem cells (iPSCs) from adult somatic cells is one of the most exciting discoveries in recent biomedical research. It holds tremendous potential in drug discovery and regenerative medicine. However, a series of reports highlighting genomic instability in iPSCs raises concerns about their clinical application. Although the mechanisms cause genomic instability during cellular reprogramming are largely unknown, several potential sources have been suggested. This review summarizes current knowledge on this active research field and discusses the latest efforts to alleviate the genomic insults during cellular reprogramming to generate iPSCs with enhanced quality and safety., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Recent studies suggest that besides the long-known farmer's lung antigen sources Saccharopolyspora rectivirgula (Micropolyspora faeni), Thermoactinomyces vulgaris, and Aspergillus fumigatus, additionally the mold Absidia (Lichtheimia) corymbifera as well as the bacteria Erwinia herbicola (Pantoea agglomerans) and Streptomyces albus may cause farmer's lung in Germany. In this study the sera of 64 farmers with a suspicion of farmer's lung were examined for the following further antigens: Wallemia sebi, Cladosporium herbarum, Aspergillus versicolor, and Eurotium amstelodami. Our results indicate that these molds are not frequent causes of farmer's lung in Germany., (© Georg Thieme Verlag KG Stuttgart · New York.)

Extrinsic allergic alveolitis (hypersensitivity pneumonitis), especially humidifier lung, has been more frequently diagnosed over the last decades, whereas farmer's lung has decreased over the same time period. Today two types of the chronic course of extrinsic allergic alveolitis can be distinguished. The recurrent chronic course with a good prognosis may be differentiated from the insidious course with a poor prognosis by means of different histological patterns (UIP, NSIP, BOOP pattern). The characteristic neutrophilic infiltration of the lung in the insidious course cannot be detected by bronchoalveolar lavage (BAL) methods. Furthermore, lymphocytosis in the BAL can be absent or present at a low level. The CD4/CD8 ratio is not always decreased and may be normal or even increased in these insidious cases with a poor prognosis. Granulomas in the lung tissue, however, point to a good prognosis. In the diagnostic work-up of machine operator's and humidifier lung, it is advisable not only to look for serum antibodies against bacteria and molds but also for rapid growing mycobacteria in a sample of machine or humidifier water. IgM and IgG rheumatoid factors occur frequently in allergic alveolitis, especially in humidifier lung. The patients, however, do not suffer from arthritis. The IgM rheumatoid factor may simulate IgM antibodies against numerous infectious agents (e. g., Bordetella pertussis or Mycoplasma pneumoniae). Taking this phenomenon into account may improve the current differential diagnosis of allergic alveolitis.

The radiologic work-up of a 67-year-old female patient for dyspnea revealed micronodular infiltrates in both lungs, which in combination with enlarged mediastinal and abdominal lymph-nodes were highly suspicious of sarcoidosis stage II. A bronchoscopic examination including transbronchial biopsy in another hospital was not diagnostic, so the patient was referred to us for surgical lung biopsy. A specimen from the right middle lobe showed massive haemangiotic carcinomatosis of a clear-cell carcinoma. The pathologist--without knowing the history of the patient--discussed a renal-cell carcinoma as potential primary malignancy, which could easily be confirmed as the patient had a tumor-nephrectomy two years ago.

In senescence renal function is thought to decline markedly even in the absence of renal disease. It has also been proposed that the changes in renal function with age are not uniform and that confounding factors such as hypertension or atherosclerosis may play a role. We performed a comprehensive study to compare several aspects of renal function in four groups: (i) young healthy normotensive subjects (N = 24; 13 males; mean age 26 +/- 3 years); (ii) elderly healthy normotensive subjects (elderly NT; N = 29; 13 males; 68 +/- 7 years); (iii) elderly treated and untreated hypertensive patients (elderly HT; N = 25; 13 males; 70 +/- 6 years); and (iv) elderly patients with compensated mild to moderate heart failure (elderly HF; N = 14; 6 males; 69 +/- 6 years). Compared to young subjects mean GFR (C(In)) and ERPF (C(PAH)) were significantly lower in the elderly, despite similar mean plasma creatinine levels (young, 121 +/- 11, 650 +/- 85 ml/min/1.73 m2; elderly NT, 103 +/- 11, 486 +/- 102; elderly HT, 103 +/- 13, 427 +/- 55; elderly HF, 92 +/- 14, 377 +/- 103). Nevertheless, GFR was within the normal range in the majority of elderly NT and HT, but not in elderly HF. ERPF was significantly lower in elderly HT as compared with elderly NT, and still lower in elderly HF. Mean renovascular resistance and filtration fraction were significantly higher in the elderly, particularly in elderly HT and HF as compared with the young. Mean fractional excretion of Na+ was similar in all groups studied, but the lithium clearance was significantly lower in the elderly, suggesting a greater proximal and less distal sodium reabsorption in senescence. In the elderly, mean PTH concentration and urinary excretion of pyridoline cross-links were significantly higher and mean 25-(OH)D3, calcitriol and phosphate concentrations significantly lower; the correlation between PTH and GFR was significant (r = -0.432, P < 0.001). The results document that the decrease in renal hemodynamics with senescence is less marked than suggested by some studies using less stringent methodology and inclusion criteria. Comorbid conditions confound renal function in the elderly. Age-associated changes in renal hemodynamics are accompanied by significant alterations of renal hormones and of renal sodium handling.