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Deutsches Arzteblatt International Apr 2024According 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. (Review)
Review
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.
Topics: Humans; Air Pollution, Indoor; Fungi; Germany; Mycoses
PubMed: 38381662
DOI: 10.3238/arztebl.m2024.0018 -
The Journal of Allergy and Clinical... Oct 2023Gain-of-function variants of JAK1 drive a rare immune dysregulation syndrome associated with atopic dermatitis, allergy, and eosinophilia.
BACKGROUND
Gain-of-function variants of JAK1 drive a rare immune dysregulation syndrome associated with atopic dermatitis, allergy, and eosinophilia.
OBJECTIVES
This study sought to describe the clinical and immunological characteristics associated with a new gain-of-function variant of JAK1 and report the therapeutic efficacy of Janus kinase (JAK) inhibition.
METHODS
The investigators identified a family affected by JAK1-associated autoinflammatory disease and performed clinical assessment and immunological monitoring on 9 patients. JAK1 signaling was studied by flow and mass cytometry in patients' cells at basal state or after immune stimulation. A molecular disease signature in the blood was studied at the transcriptomic level. Patients were treated with 1 of 2 JAK inhibitors: either baricitinib or upadacitinib. Clinical, cellular, and molecular response were evaluated over a 2-year period.
RESULTS
Affected individuals displayed a syndromic disease with prominent allergy including atopic dermatitis, ichthyosis, arthralgia, chronic diarrhea, disseminated calcifying fibrous tumors, and elevated whole blood histamine levels. A variant of JAK1 localized in the pseudokinase domain was identified in all 9 affected, tested patients. Hyper-phosphorylation of STAT3 was found in 5 of 6 patients tested. Treatment of patients' cells with baricitinib controlled most of the atypical hyper-phosphorylation of STAT3. Administration of baricitinib to patients led to rapid improvement of the disease in all adults and was associated with reduction of systemic inflammation.
CONCLUSIONS
Patients with this new JAK1 gain-of-function pathogenic variant displayed very high levels of blood histamine and showed a variable combination of atopy with articular and gastrointestinal manifestations as well as calcifying fibrous tumors. The disease, which appears to be linked to STAT3 hyperactivation, was well controlled under treatment by JAK inhibitors in adult patients.
Topics: Adult; Humans; Janus Kinase Inhibitors; Dermatitis, Atopic; Histamine; Neoplasms; Janus Kinase 1
PubMed: 37343845
DOI: 10.1016/j.jaci.2023.06.004 -
The European Respiratory Journal Nov 2023Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To... (Observational Study)
Observational Study
BACKGROUND
Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings.
METHODS
First, we conducted an observational study using UK medical records to match asthma patients 1:1, by age, sex and general practitioner (GP) practice, to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium (TAGC) and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium (CARDIoGRAM). Using 64 asthma single nucleotide polymorphisms, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy.
RESULTS
In our observational study (n=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR 1.06, 95% CI 1.01-1.13); after accounting for healthcare behaviour, we found no association (model 2: HR 0.99, 95% CI 0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR 1.11, 95% CI 1.01-1.21; males: HR 0.91, 95% CI 0.84-0.98). Our MR study (n=589 875) found no association between asthma and CHD (OR 1.01, 95% CI 0.98-1.04) and no modification by sex.
CONCLUSIONS
Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.
Topics: Female; Humans; Male; Analysis of Variance; Asthma; Coronary Artery Disease; Genome-Wide Association Study; Myocardial Infarction; Polymorphism, Single Nucleotide; Risk Factors; Mendelian Randomization Analysis
PubMed: 37945032
DOI: 10.1183/13993003.01788-2023 -
Nature Communications Oct 2023Liver fibrosis results from chronic liver injury triggered by factors such as viral infection, excess alcohol intake, and lipid accumulation. However, the mechanisms...
Liver fibrosis results from chronic liver injury triggered by factors such as viral infection, excess alcohol intake, and lipid accumulation. However, the mechanisms underlying liver fibrosis are not fully understood. Here, we demonstrate that the expression of fibroblast growth factor 18 (Fgf18) is elevated in mouse livers following the induction of chronic liver fibrosis models. Deletion of Fgf18 in hepatocytes attenuates liver fibrosis; conversely, overexpression of Fgf18 promotes liver fibrosis. Single-cell RNA sequencing reveals that overexpression of Fgf18 in hepatocytes results in an increase in the number of Lrat hepatic stellate cells (HSCs), thereby inducing fibrosis. Mechanistically, FGF18 stimulates the proliferation of HSCs by inducing the expression of Ccnd1. Moreover, the expression of FGF18 is correlated with the expression of profibrotic genes, such as COL1A1 and ACTA2, in human liver biopsy samples. Thus, FGF18 promotes liver fibrosis and could serve as a therapeutic target to treat liver fibrosis.
Topics: Mice; Animals; Humans; Hepatic Stellate Cells; Liver Cirrhosis; Liver; Fibrosis; Cell Proliferation
PubMed: 37813881
DOI: 10.1038/s41467-023-42058-z -
Biomedicines Nov 2023(1) Background: "Brittle Asthma" was considered an asthma clinical phenotype and deemed to be life-threatening in the early 2000s; then, this definition disappeared. The... (Review)
Review
(1) Background: "Brittle Asthma" was considered an asthma clinical phenotype and deemed to be life-threatening in the early 2000s; then, this definition disappeared. The purpose of this review is to examine what has historically been referred to as this term and see whether it may be applied to modern clinical practice, thus acquiring fresh relevance and meaning. (2) Methods: A non-systematic search of the literature was conducted using both MeSH and free-text phrases. No limitations on the research design or type of publication were applied. (3) Results: Reliable data regarding "Brittle Asthma" are lacking due to the paucity of current data and the few studies available. After a few years of reworking, it was divided into two sub-classes: one characterized by a wide PEF variability despite high-dose therapy and the other by sudden acute attacks in otherwise apparently normal airway functions or well-controlled asthma. Their characteristics were hardly defined because of their low prevalence. Data regarding risk factors, atopy, mechanisms, and treatments were analyzed. (4) Conclusions: Over time, different terminology has been introduced to define asthma severity and control. It would be worth investigating whether the term "Brittle Asthma" previously used may be helpful to find new hints to stratify patients and improve disease management.
PubMed: 38002086
DOI: 10.3390/biomedicines11113086