Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

Canine scent detection for the diagnosis of lung cancer in a screening-like situation

The prognosis in lung cancer depends largely on early stage detection, and thus new screening methods are attracting increasing attention. Canine scent detection has shown promising results in lung cancer detection, but there has only been one previous study that reproduces a screening-like situation. Here breath samples were collected from 122 patients at risk for lung cancer (smokers and ex-smokers); 29 of the subjects had confirmed diagnosis of lung cancer but had not yet been treated and 93 subjects had no signs or symptoms of lung cancer at the time of inclusion. The breath samples were presented to a trained sniffer dog squadron in a double-blind manner. A rigid scientific protocol was used with respect to earlier canine scent detection studies, with one difference: instead of offering one in five positive samples to the dogs, we offered a random number of positive samples (zero to five). The final positive and negative predictive values of 30.9% and 84.0%, respec tively, were rather low compared to other studies. The results differed from those of previous studies, indicating that canine scent detection might not be as powerful as is looked for in real screening situations. One main reason for the rather poor performance in our setting might be the higher stress from the lack of positive responses for dogs and handlers

Diagnostische Leistungsbeurteilung zweier kommerziell erhältlicher Schnelltests zum Nachweis von IgG und IgM Antikörper gegen SARS-CoV-2 im Vergleich zu ELISA in einer niedrigprävalenz-Population

Background: New commercially available point-of-care (POC) immunodiagnostic tests are appearing, which may yield rapid results for anti-SARS-CoV-2 antibodies. The aim of this study was to evaluate the diagnostic accuracy of rapid antibody detection tests compared to a validated laboratory-based enzyme-linked immunosorbent assay (ELISA) and to investigate infections amongst healthcare workers (HCWs) after unprotected close contact to COVID-19 patients. Methods: Blood serum and whole blood of 130 participants were tested with NADAL® COVID-19 IgG/IgM rapid test and mö-screen 2019-NCOV coronavirus test against a validated ELISA test. Infection status was evaluated using real-time polymerase-chain-reaction.Results: Acute COVID-19 infection was detected in 2.4% of exposed HCWs. Antibody tests showed an overall frequency of IgG and IgM in 5.3%, with 1.6% asymptomatic infections. The NADAL® test showed a sensitivity (IgM/IgG) of 100% (100%/100%), a specificity (IgM/IgG) of 98.8% (97.6%/100 %), a PPV of 76.9% (57.1%/100%), an NPV of 100% (100%/100%), and a diagnostic accuracy of 98.8% (97.7%/100%). The mö-screen test had a sensitivity (IgM/IgG) of 90.9% (80%/100%), a specificity (IgM/IgG) of 98.8% (97.6%/100%), a PPV of 76.9% (57.1%/100%), an NPV of 99.6% (99.2%/100%), and a diagnostic accuracy of 98.5% (96.9%/100%). Conclusions: The frequency of COVID-19 infections in HCWs after unprotected close contact is higher than in the general population of a low-prevalence country. Both POC tests were useful for detecting IgG, but did not perform well for IgM, mainly due to false positive results.Hintergrund: Es erscheinen neue im Handel erhältliche immundiagnostische Point-of-Care-Tests (POC), die schnelle Ergebnisse für Anti-SARS-CoV-2-Antikörper liefern können. Ziel dieser Studie war es, die diagnostische Leistungsfähigkeit von Schnelltests zum Nachweis von Antikörpern im Vergleich zu einem validierten ELISA (Enzyme-Linked Immunosorbent Assay) zu bewerten und Infektionen bei Beschäftigten im Gesundheitswesen nach ungeschütztem engen Kontakt mit COVID-19-Patienten zu detektieren.Methoden: Blutserum und Vollblut von 130 Teilnehmern wurden mit dem NADAL® COVID-19 IgG/IgM-Schnelltest und dem Mö-screen 2019-NCOV Coronavirus-Test gegen einen validierten ELISA-Test untersucht. Der Infektionsstatus wurde unter Verwendung einer Echtzeit-Polymerase-Kettenreaktion (RT-PCR) bewertet.Ergebnisse: Eine akute COVID-19-Infektion wurde bei 2,4% der exponierten Mitarbeiterinnen festgestellt. Antikörpertests zeigten eine Gesamthäufigkeit von IgG und IgM in 5,3% bei 1,6% asymptomatischen Infektionen. Der NADAL®-Test zeigte eine Sensitivität (IgM/IgG) von 100% (100%/100%), eine Spezifität (IgM/IgG) von 98,8% (97,6%/100%), einen PPV von 76,9% (57,1%/100%), ein NPV von 100% (100%/100%) und eine diagnostische Genauigkeit von 98,8% (97,7%/100%). Der Mö-Screen-Test hatte eine Sensitivität (IgM/IgG) von 90,9% (80%/100%), eine Spezifität (IgM/IgG) von 98,8% (97,6%/100%), einen PPV von 76,9% (57,1%/100%), ein Kapitalwert von 99,6% (99,2%/100%) und eine diagnostische Genauigkeit von 98,5% (96,9%/100%).Schlussfolgerung: Die Häufigkeit von COVID-19-Infektionen bei Mitarbeitern im Gesundheitswesen nach ungeschütztem engem Kontakt ist höher als in der Allgemeinbevölkerung eines Landes mit niedriger Prävalenz. Beide POC-Tests waren zum Nachweis von IgG nützlich, zeigten jedoch keine gute Leistungsfähigkeit für den Nachweis von IgM, hauptsächlich aufgrund falsch positiver Ergebnisse

Microarray technology may reveal the contribution of allergen exposure and rhinovirus infections as possible triggers for acute wheezing attacks in preschool children

Allergen exposure and rhinovirus (RV) infections are common triggers of acute wheezing exacerbations in early childhood. The identification of such trigger factors is difficult but may have therapeutic implications. Increases of IgE and IgG in sera, were shown against allergens and the N-terminal portion of the VP1 proteins of RV species, respectively, several weeks after allergen exposure or RV infection. Hence, increases in VP1-specific IgG and in allergen-specific IgE may serve as biomarkers for RV infections or allergen exposure. The MeDALL-allergen chip containing comprehensive panels of allergens and the PreDicta RV chip equipped with VP1-derived peptides, representative of three genetic RV species, were used to measure allergen-specific IgE levels and RV-species-specific IgG levels in sera obtained from 120 preschool children at the time of an acute wheezing attack and convalescence. Nearly 20% of the children (22/120) showed specific IgE sensitizations to at least one of the allergen molecules on the MeDALL chip. For 87% of the children, increases in RV-specific IgG could be detected in the follow-up sera. This percentage of RV-specific IgG increases was equal in IgE-positive and-negative children. In 10% of the children, increases or de novo appearances of IgE sensitizations indicative of allergen exposure could be detected. Our results suggest that, in the majority of preschool children, RV infections trigger wheezing attacks, but, in addition, allergen exposure seems to play a role as a trigger factor. RV-induced wheezing attacks occur in IgE-sensitized and non-IgE-sensitized children, indicating that allergic sensitization is not a prerequisite for RV-induced wheeze. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Toward personalization of asthma treatment according to trigger factors

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma. © 2020 The Author

Toward personalization of asthma treatment according to trigger factors

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma