Effect of antigen removal in hypersensitivity pneumonitis
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ABSTRACT:
SUBMITTER: Robertshaw M
PROVIDER: S-EPMC11337626 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundExposure assessment is integral to the diagnosis of hypersensitivity pneumonitis (HP). Although the clinical relevance of exposed antigens is essential for the assessment, many of the previous guidelines or reports have only evaluated simple exposure histories or immunological tests. To overcome this problem, the Exposure Assessment Form (EAF) was developed as an assessment tool for classifying the exposure grade from G0 to G4. The EAF was modified from the description in the Japanese clinical practice guide 2022 for HP published by the Japanese Respiratory Society.MethodsOne hundred and seventy-two consecutive patients with interstitial lung disease who underwent multidisciplinary discussion (MDD) at our hospital were retrospectively examined. We assessed whether the use of the EAF improved the diagnostic performance of the international guideline of HP. We also evaluated whether the exposure grade affected the prognosis of HP.ResultsEven when a HP diagnosis was made with a confidence of 70% or higher according to the international guideline, less than half of these cases resulted in a final diagnosis of HP when the exposure grades were lower than G3. When the result of the EAF was integrated into the exposure definition of the international guideline, the specificity of the diagnostic performance improved, while sensitivity was maintained. Furthermore, HP patients with an exposure grade of G3 or higher showed a tendency to take a longer time to initiate medication.ConclusionsThis is the first study to evaluate the clinical relevance of possible antigens using the EAF. Assessing the exposure grade prevents overdiagnosis and improves the diagnostic performance of the international guideline.
| S-EPMC10865633 | biostudies-literature
Project description:BackgroundAvian antigen is a common cause of hypersensitivity pneumonitis (HP). Inhalation challenge with pigeon serum and pigeon dropping extract (PDE) elicits a hypersensitivity reaction in patients with bird-related hypersensitivity pneumonitis (BRHP), but the antigenic components in these materials have yet to be fully elucidated.MethodPigeon serum, pigeon intestine homogenates, and PDE were immunoblotted with serum samples from 8 patients with BRHP, 2 patients with summer-type HP, 2 patients with humidifier lung, and 3 healthy volunteers. Among the protein spots found in both pigeon serum and PDE, those that reacted with sera from BRHP patients were identified by mass spectrometry. Immunoassays using recombinant protein were performed to confirm the antigenicity of the identified protein. Cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant protein was also assessed.ResultsImmunoglobulin lambda-like polypeptide-1 (IGLL-1) was identified from all spots on 2-DE immunoblots of both pigeon serum and PDE. The BRHP patients exhibited higher levels of serum IgG antibody against the recombinant IGLL-1 (rIGLL-1) compared to the control subjects, as well as a stronger PBMCs proliferative response to rIGLL-1. Cytokine production by PBMCs from BRHP patients after rIGLL-1 exposure indicated that the protein could induce Th1 prone immune responses: an increase in TNF-α and an absence of elevated IL-10 production.ConclusionsPigeon IGLL-1 was identified as the BRHP antigen present in both pigeon serum and PDE.
| S-EPMC5397797 | biostudies-literature
Project description:BACKGROUND:In chronic hypersensitivity pneumonitis (chronic HP), antigen avoidance is critical for disease management; however, complete avoidance is difficult because of unrecognized exposure to antigens. Recently, we revealed that the amount of avian antigen (AAA) in household dust at the time of diagnosis predicted the progression of chronic bird-related HP. The purpose of this study is to evaluate the relationship between the prognosis of chronic bird-related HP and the AAA that remained in the environment during antigen avoidance. METHODS:First, we measured the AAA in household dust of 28 consecutive patients (22 with chronic bird-related HP and 6 with acute bird-related HP) and 12 healthy volunteers. Second, we measured the AAA and collected questionnaires on the environmental conditions of the homes of 53 patients with various lung diseases, including bird-related HP, to investigate the environmental parameters related to a higher AAA. Finally, we prospectively recruited 14 consecutive patients with chronic bird-related HP, measured the AAA periodically, and collected clinical data. RESULTS:The AAA was higher in patients with chronic bird-related HP at the time of diagnosis compared to healthy volunteers and was highest in patients with acute bird-related HP. Logistic regression analysis showed that birds frequenting a residence was the only significant factor for a higher AAA (odds ratio, 5.686; 95%CI, 1.263-25.59; P = 0.024). There was a correlation between the mean AAA and decline of vital capacity for 1 year (r = -0.55; 95%CI -0.84 to -0.01; P = 0.043). CONCLUSION:Measurements of the AAA after diagnosis predict the progression of chronic bird-related HP. Avian antigen can exist in the indoor environment regardless of antigen avoidance. The presence of avian antigen in the indoor environment can be attributed to wild birds found outdoors.
| S-EPMC5818447 | biostudies-literature
Project description:BackgroundChronic hypersensitivity pneumonitis (CHP) is an interstitial lung disease (ILD) caused by long term exposure to an offending antigen. Antigen avoidance is associated with improved outcomes. We are unable to identify the antigen source in approximately half of patients. When an antigen is successfully identified, patients have difficulty with avoidance.MethodsWe conducted three structured group discussions with US based ILD specialists utilizing the nominal group technique (NGT). Participants listed barriers to antigen detection and avoidance in CHP. Each participant ranked what they perceived to be the top three barriers in the list in terms of importance. The master list of barriers was consolidated across the three groups into themes that were prioritized based on receiving the highest rankings by participants.ResultsTwenty-five physicians participated; 56% had experience caring for CHP patients for ≥ 16 years. Sixty barriers to antigen detection were categorized into seven themes of which the top three were: 1. unclear significance of identified exposures; 2. gaps in clinical knowledge and testing capabilities; 3. there are many unknown and undiscovered antigens. Twenty-eight barriers to antigen avoidance were categorized into five themes of which the top three were: 1. patient limitations, financial barriers and lack of resources; 2. individual patient beliefs, emotions and attachments to the antigen source; and 3. gaps in clinical knowledge and testing capabilities.ConclusionsThis study uncovered challenges at the individual patient, organizational, and societal levels and ranked them in terms of level of importance. These findings provide information to guide development and validation of multidisciplinary support and interventions geared towards antigen identification and avoidance in CHP.
| S-EPMC8353836 | biostudies-literature
Project description: Not available
| S-EPMC6888653 | biostudies-literature
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.
| S-EPMC4451710 | biostudies-literature
Project description:BackgroundHypersensitivity pneumonitis (HP) is an immune-mediated disorder that causes inflammation of interstitial lung, bronchioles, and alveoli. Although corticosteroids have been used as first line treatment for HP for many years, it does not provide satisfactory results in all patients. The aim of this study is to compare the effect of oral methylprednisolone on different radiological patterns of HP to identify the most adequate candidates for corticosteroids.Patients and methodsFifty-three patients with confirmed diagnosis of HP were divided into two groups according to their radiological patterns based on high resolution computed tomography (HRCT) findings. The first group included 21 patients with fibrotic HP (fHP), the second group included 32 patients without fibrosis; non-fibrotic HP patients (nfHP). The second group is divided into 3 subgroups: mosaic, attenuation, centrilobular nodules and finally, ground-glass opacities. All patients were administered methylprednisolone by dose 0.5mg/kg/day for eight consecutive weeks. HRCT was performed at the beginning of the study. Spirometry, six-minute walk and oximetry were performed periodically to assess the patients' progress.ResultsUpon finalizing the treatment process, a significant improvement was noticed in FEV1 (p < 0.001), FVC (p <0.001), six-minute walk test (p =0.001) and oximetry (p <0.05) in nfHP compared to the fHP patients. However, there was a significant improvement in (p <0.01), FVC (p <0.01), oximetry (p <0.01) and six-minute walk test (p <0.01) in fibrotic patients after receiving the treatment. There was no significant difference in the response of FEV1 (p =0.82), FVC (p =0.15), six-minute walk test (p =0.36) and oximetry (p =0.27) among the subgroups of nfHP patients.ConclusionIt was accordingly concluded that corticosteroid treatment is more effective in treatment of nfHP than fHP patients but still has effect on fibrotic patients. There is no significant difference in the response to corticosteroids among nfHP patients' subgroups.
| S-EPMC8121673 | biostudies-literature
Project description:BackgroundIdentification of inciting antigen can affect diagnostic confidence, quality of life, and prognosis in patients with HP. It is unknown whether the number and type of antigen affect results of diagnostic testing or prognosis, whether antigen identified by clinical history alone affects prognosis, and whether feather exposure is associated with outcomes similar to those of other antigens.MethodsTo evaluate whether the number or type of antigen identified by clinical history alone affects clinical outcomes, we evaluated a retrospective cohort of patients with a high or definite probability of HP based on recent guidelines.ResultsIn our retrospective cohort, 136 patients met high or definite probability of HP and were included in the analysis. Median transplant-free survival was better in patients with antigen identified on clinical history alone than patients without identified antigen. Feather exposure was associated with improved TFS compared to patients without antigen identified; there was no difference in TFS between patients with feather exposure and either mold or live bird exposure. Mold antigen was associated with increased risk of fibrotic HP compared to avian antigen. Among patients with identified antigen, the number and type of antigen did not affect TFS.DiscussionOur study suggests that clinical history is adequate for providing prognostic information to patients with HP and classifying the diagnostic probability of HP according to recent guidelines. Feather exposure should be considered an inciting antigen in patients with ILD.
| S-EPMC9436128 | biostudies-literature
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
Project description:Bird-related hypersensitivity pneumonitis (BRHP) is an interstitial lung disease induced by avian proteins. The immunopathological pathways involved in the disease are still unknown. This study assesses the cellular immune response and the cytokine pattern in a mouse model of BRHP. On days -3 and -1, mice were intraperitoneally sensitized with commercial pigeon serum (PS) or saline. Intranasal instillations with PS or saline were carried out on three consecutive days/week over either 3 weeks (Group 1) or 12 weeks (Group 2). Leukocyte and cytokine patterns in lung tissue and pulmonary inflammation in bronchoalveolar lavage (BAL) were analysed. Both groups presented increases in resident monocytes, interstitial macrophages and type 2 dendritic cells (DCs), but also reductions in inflammatory monocytes, alveolar macrophages and tolerogenic DCs compared with their control groups. Group 1 had increased levels of eosinophils and T cells with reductions in neutrophils and B cells, while Group 2 showed high levels of B cells. Both groups exhibited increases in Th1 and Th2 cytokines. Group 2 also showed increased levels of IL-23, a Th17 cytokine. Increased levels of neutrophils, eosinophils and lymphocytes were observed in BAL samples of both groups compared with controls. In the first stages of BRHP, there is a mixed Th1/Th2 immune response, while during the progression of the disease, although there is a Th1 response, the cytokine levels seem to indicate a switch towards a Th2/Th17 mixed response.
| S-EPMC9917634 | biostudies-literature