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Development of a Diagnostic Biosensor Method of Hypersensitivity Pneumonitis towards a Point-of-Care Biosensor.

ABSTRACT: In spite of a current increasing trend in the development of miniaturized, standalone point-of-care (PoC) biosensing platforms in the literature, the actual implementation of such systems in the field is far from being a reality although deeply needed. In the particular case of the population screenings for local or regional diseases related to specific pathogens, the diagnosis of the presence of specific antibodies could drastically modify therapies and even the organization of public policies. The aim of this work was to develop a fast, cost-effective detection method based on the manipulation of functionalized magnetic beads for an efficient diagnosis of hypersensitivity pneumonitis (HP), looking for the presence of anti-pigeon antigen antibodies (APAA) in a patient's serum. We presented a Diagnostic Biosensor Method (DBM) in detail, with validation by comparison with a traditional high-throughput platform (ELISA assay). We also demonstrated that it was compatible with a microfluidic chip that could be eventually incorporated into a PoC for easy and broad deployment using portable optical detectors. After standardization of the different reaction steps, we constructed and validated a plastic chip that could easily be scaled to high-volume manufacturing in the future. The solution proved comparable to conventional ELISA assays traditionally performed by the clinicians in their laboratory and should be compatible with other antibody detection directly from patient samples.

SUBMITTER: Fiordelisio T

PROVIDER: S-EPMC8232117 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Hypersensitivity Pneumonitis: Diagnostic and Therapeutic Challenges.

Project description:Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases (ILD), that presents unique challenges for a confident diagnosis and limited therapeutic options. The disease is triggered by exposure to a wide variety of inciting antigens in susceptible individuals which results in T-cell hyperactivation and bronchioloalveolar inflammation. However, the genetic risk and the pathogenic mechanisms remain incompletely elucidated. Revised diagnostic criteria have recently been proposed, recommending to classify the disease in fibrotic and non-fibrotic HP which has strong therapeutic and outcome consequences. Confident diagnosis depends on the presence of clinical features of ILD, identification of the antigen(s), typical images on high-resolution computed tomography (HRCT), characteristic histopathological features, and lymphocytosis in the bronchoalveolar lavage. However, identifying the source of antigen is usually challenging, and HRCT and histopathology are often heterogeneous and not typical, supporting the notion that diagnosis should include a multidisciplinary assessment. Antigen removal and treating the inflammatory process is crucial in the progression of the disease since chronic persistent inflammation seems to be one of the mechanisms leading to lung fibrotic remodeling. Fibrotic HP has a few therapeutic options but evidence of efficacy is still scanty. Deciphering the molecular pathobiology of HP will contribute to open new therapeutic avenues and will provide vital insights in the search for novel diagnostic and prognostic biomarkers.

| S-EPMC8495410 | biostudies-literature

Characteristics of a diagnostic bronchoscopy in hypersensitivity pneumonitis.

Project description:BackgroundBronchoalveolar lavage and transbronchial biopsy can increase diagnostic confidence in the diagnosis of hypersensitivity pneumonitis (HP). Improving the yield of bronchoscopy may help to improve diagnostic confidence while decreasing the risk of potential adverse outcomes associated with more invasive procedures such as surgical lung biopsy. The purpose of this study is to identify factors that were associated with a diagnostic BAL or TBBx in HP.MethodsWe conducted a retrospective cohort study of HP patients at a single center who underwent bronchoscopy during the diagnostic evaluation. Imaging characteristics, clinical characteristics including use of immunosuppressive medications and presence of active antigen exposure at the time of bronchoscopy, and procedural characteristics were collected. Univariable and multivariable analysis was performed.Results88 patients were included in the study. 75 patients underwent BAL and 79 patients underwent TBBx. Patients who had an active fibrogenic exposure at the time of bronchoscopy had a higher BAL yield than those who were out of exposure at the time of bronchoscopy. TBBx yield was higher when more than 1 lobe was biopsied, with a trend toward higher yield of TBBx when nonfibrotic lung was biopsied compared to fibrotic lung.DiscussionOur study suggests characteristics that may improve yield of BAL and TBBx in patients with HP. We suggest that bronchoscopy be performed when patients are in the antigen exposure and that TBBx samples are taken from more than 1 lobe in order to improve diagnostic yield of the procedure.

| S-EPMC10191301 | biostudies-literature

Quantification of cDNA on GMR biosensor array towards point-of-care gene expression analysis.

Project description:Gene expression analysis at the point-of-care is important for rapid disease diagnosis, but traditional techniques are limited by multiplexing capabilities, bulky equipment, and cost. We present a gene expression analysis platform using a giant magnetoresistive (GMR) biosensor array, which allows multiplexed transcript detection and quantification through cost-effective magnetic detection. In this work, we have characterized the sensitivity, dynamic range, and quantification accuracy of Polymerase chain reaction (PCR)-amplified complementary DNA (cDNA) on the GMR for the reference gene GAPDH. A synthetic GAPDH single-stranded DNA (ssDNA) standard was used to calibrate the detection, and ssDNA dilutions were qPCR-amplified to obtain a standard curve. We demonstrate that the GMR platform provides a dynamic range of 4 orders of magnitude and a limit of detection of 1?pM and 0.1?pM respectively for 15 and 18-cycle amplified synthetic GAPDH PCR products. The quantitative results of GMR analysis of cell-line RNA were confirmed by qPCR.

| S-EPMC6391206 | biostudies-literature

Assessment of clinical relevance of antigen improves diagnostic accuracy of hypersensitivity pneumonitis

Project description: Not available

| S-EPMC10865633 | biostudies-literature

Development of a Knowledge-sharing Website for Hypersensitivity Pneumonitis Exposures.

Project description:BackgroundIdentification of potential inciting antigens known to be associated with hypersensitivity pneumonitis (HP) is integral to achieving a confident diagnosis, its management, and prognostication. A barrier to achieving diagnostic confidence is that evidence for exposure assessment is not presented in an easily accessible or useful format.ObjectiveTo develop a freely available comprehensive living repository of contemporaneous exposures associated with HP.MethodsElectronic searches were performed through Medline, Embase, and Web of Science from January 1, 2002, to December 31, 2019, using the following broad MeSH headings: ([allerg* or hypersensitiv*], and adj [alveol* or pneumo*]).mp. Articles were included if they described adults or children with a diagnosis of HP (as defined by authors) and a description of the causative exposure. Website development used a structured query language database and was powered by WordPress.ResultsHPLung.com is a freely available online searchable repository that lists all exposures and antigens associated with HP and links to their parent studies. Eighty-five unique exposures from 447 citations have been included thus far. The website continues to be updated iteratively. Since its launch in 2019, HPLung.com has been visited over 4,500 times by users from 75 different countries.ConclusionHPLung.com is a novel knowledge-sharing tool that addresses barriers of accessibility, contemporaneity, efficient evidence synthesis, and making the best use of technological platforms to improve the exposure assessment of those suspected of HP.

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Development and validation of a radiological diagnosis model for hypersensitivity pneumonitis.

Project description:High-resolution computed tomography (HRCT) may be useful for diagnosing hypersensitivity pneumonitis. Here, we develop and validate a radiological diagnosis model and model-based points score.Patients with interstitial lung disease seen at the University of Michigan Health System (derivation cohort) or enrolling in the Lung Tissue Research Consortium (validation cohort) were included. A thin-section, inspiratory HRCT scan was required. Thoracic radiologists documented radiological features.The derivation cohort comprised 356 subjects (33.9% hypersensitivity pneumonitis) and the validation cohort comprised 424 subjects (15.5% hypersensitivity pneumonitis). An age-, sex- and smoking status-adjusted logistic regression model identified extent of mosaic attenuation or air trapping greater than that of reticulation ("MA-AT>Reticulation"; OR 6.20, 95% CI 3.53-10.90; p<0.0001) and diffuse axial disease distribution (OR 2.33, 95% CI 1.31-4.16; p=0.004) as hypersensitivity pneumonitis predictors (area under the receiver operating characteristic curve 0.814). A model-based score >2 (1 point for axial distribution, 2 points for "MA-AT>Reticulation") has specificity 90% and positive predictive value (PPV) 74% in the derivation cohort and specificity 96% and PPV 44% in the validation cohort. Similar model performance is seen with population restriction to those reporting no exposure (score >2: specificity 91%).When radiological mosaic attenuation or air trapping are more extensive than reticulation and disease has diffuse axial distribution, hypersensitivity pneumonitis specificity is high and false diagnosis risk low (<10%), but PPV is diminished in a low-prevalence setting.

| S-EPMC6181129 | biostudies-literature

Telomeropathy in Chronic Hypersensitivity Pneumonitis.

Project description: Not available

| S-EPMC6888653 | biostudies-literature

Lung transplantation for hypersensitivity pneumonitis.

Project description:BackgroundHypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF).MethodsTo identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling.ResultsWe analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts.ConclusionsOverall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft.

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Novel Point-of-Care Diagnostic Method for Neonatal Encephalopathy Using Purine Nucleosides.

Project description:Background: Evidence suggests that earlier diagnosis and initiation of treatment immediately after birth is critical for improved neurodevelopmental outcomes following neonatal encephalopathy (NE). Current diagnostic tests are, however, mainly restricted to clinical diagnosis with no molecular tests available. Purines including adenosine are released during brain injury such as hypoxia and are also present in biofluids. Whether blood purine changes can be used to diagnose NE has not been investigated to date. Methods: Blood purines were measured in a mouse model of neonatal hypoxia and infants with NE using a novel point-of-care diagnostic technology (SMARTChip) based on the summated electrochemical detection of adenosine and adenosine metabolites in the blood. Results: Blood purine concentrations were ∼2-3-fold elevated following hypoxia in mice [2.77 ± 0.48 μM (Control) vs. 7.57 ± 1.41 μM (post-hypoxia), p = 0.029]. Data in infants with NE had a 2-3-fold elevation when compared to healthy controls [1.63 ± 0.47 μM (Control, N = 5) vs. 4.87 ± 0.92 μM (NE, N = 21), p = 0.0155]. ROC curve analysis demonstrates a high sensitivity (81%) and specificity (80%) for our approach to identify infants with NE. Moreover, blood purine concentrations were higher in infants with NE and seizures [8.13 ± 3.23 μM (with seizures, N = 5) vs. 3.86 ± 0.56 μM (without seizures, N = 16), p = 0.044]. Conclusion: Our data provides the proof-of-concept that measurement of blood purine concentrations via SMARTChip technology may offer a low-volume bedside test to support a rapid diagnosis of NE.

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ITK independent development of Th17 responses during hypersensitivity pneumonitis driven lung inflammation.

Project description:T helper 17 (Th17) cells develop in response to T cell receptor signals (TCR) in the presence of specific environments, and produce the inflammatory cytokine IL17A. These cells have been implicated in a number of inflammatory diseases and represent a potential target for ameliorating such diseases. The kinase ITK, a critical regulator of TCR signals, has been shown to be required for the development of Th17 cells. However, we show here that lung inflammation induced by Saccharopolyspora rectivirgula (SR) induced Hypersensitivity pneumonitis (SR-HP) results in a neutrophil independent, and ITK independent Th17 responses, although ITK signals are required for γδ T cell production of IL17A. Transcriptomic analysis of resultant ITK independent Th17 cells suggest that the SR-HP-induced extrinsic inflammatory signals may override intrinsic T cell signals downstream of ITK to rescue Th17 responses in the absence of ITK. These findings suggest that the ability to pharmaceutically target ITK to suppress Th17 responses may be dependent on the type of inflammation.

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