Hypersensitivity Pneumonitis Patients Research Articles

Increased ER Stress and Unfolded Protein Response Activation in Epithelial and Inflammatory Cells in Hypersensitivity Pneumonitis.

Several types of cytotoxic insults disrupt endoplasmic reticulum (ER) homeostasis, cause ER stress, and activate the unfolded protein response (UPR). The role of ER stress and UPR activation in hypersensitivity pneumonitis (HP) has not been described. HP is an immune-mediated interstitial lung disease that develops following repeated inhalation of various antigens in susceptible and sensitized individuals. The aim of this study was to investigate the lung expression and localization of the key effectors of the UPR, BiP/GRP78, CHOP, and sXBP1 in HP patients compared with control subjects. Furthermore, we developed a mouse model of HP to determine whether ER stress and UPR pathway are induced during this pathogenesis. In human control lungs, we observed weak positive staining for BiP in some epithelial cells and macrophages, while sXBP1 and CHOP were negative. Conversely, strong BiP, sXBP1- and CHOP-positive alveolar and bronchial epithelial, and inflammatory cells were identified in HP lungs. We also found apoptosis and autophagy markers colocalization with UPR proteins in HP lungs. Similar results were obtained in lungs from an HP mouse model. Our findings suggest that the UPR pathway is associated with the pathogenesis of HP.

Vascular endothelial growth factor in hypersensitivity pneumonitis and connective tissue disease-associated interstitial lung disease

BackgroundA growing evidence on the role of vascular endothelial growth factor (VEGF) in the pathogenesis of interstitial lung diseases accumulated over the past decade; with the development of nintedanib for the treatment of fibrotic interstitial lung diseases, our aim was to quantify serum levels of VEGF in patients’ hypersensitivity pneumonitis (HP) and connective tissue disease-associated interstitial lung diseases (CTD-ILD) with an assessment of its relationship with functional status parameters and echocardiographic findings.MethodsSpirometry, 6-min walking test, echocardiography, and serum VEGF levels were assessed in HP and CTD-ILD patients.ResultsThe study included 31 HP patients, 30 CTD-ILD patients, and 29 control subjects. VEGF level was significantly higher in HP patients than in patients with CTD-ILD and control subjects. VEGF level showed positive correlation with 6-min walk distance and forced vital capacity percent predicted and inverse correlation with percent desaturation in 6-min walk test, dyspnea score, and echocardiographic findings in both groups.ConclusionSerum VEGF is higher in HP patients than in patients with CTD-ILD and control.

The effectiveness and pharmacoeconomic study of using different corticosteroids in the treatment of hypersensitivity pneumonitis

PurposeInterstitial lung diseases (ILDs) are caused by inflammation and/or fibrosis of alveolar walls resulting in impaired gas exchange. Hypersensitivity pneumonitis (HP) is the third most common type of ILDs. Corticosteroids are the mainstay treatment for HP. The use of intramuscular (IM) betamethasone or intravenous (IV) dexamethasone as weekly pulse doses has shown higher benefit than daily oral prednisolone for HP patients. The aim of this study is to directly compare different corticosteroids in terms of effectiveness and in monetary values and perform an economic evaluation.MethodsOne hundred and seven patients were tested for pulmonary function tests (PFTs) and inflammatory markers to assess the treatment effectiveness. A cost-effectiveness analysis (CEA) was performed. ICERs between 3 treatment groups were calculated.ResultsPost treatment, Krebs von den Lungen-6 (KL-6) levels significantly improved in betamethasone group from 723.22 ± 218.18 U/ml to 554.48 ± 129.69 U/ml (p = 0.001). A significant improvement in erythrocyte sedimentation rate (ESR) occurred in the dexamethasone group from 56.12 ± 27.97 mm to 30.06 ± 16.04 mm (p = 0.048). A significant improvement in forced expiratory volume (FEV1), forced vital capacity (FVC) and six-minute walk distance (6MWD) was observed within the three treatment groups. A significant improvement in oxygen desaturation percentage (SpO2) occurred within dexamethasone and betamethasone groups. Betamethasone and dexamethasone were found more cost-effective than prednisolone as their ICERs fell in quadrant C. Furthermore, ICER between betamethasone and dexamethasone was performed; a small difference in cost was found compared to the higher benefit of betamethasone.ConclusionBetamethasone and dexamethasone were found to be more effective than prednisolone in improving the inflammatory reaction and the clinical features of HP patients. Betamethasone was found to be the best intervention in terms of cost against the effect.

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

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.

Pulmonary Function and Diffusing Capacity of Carbon Monoxide in Hypersensitivity Pneumonitis: An Observational Study of 152 Patients.

Hypersensitivity pneumonitis (HP) is an inflammatory and/or fibrotic lung disease. The restrictive lung function with low diffusing capacity of carbon monoxide (DLCO) is common in interstitial lung diseases (ILD). There are limited data on pulmonary function test (PFT) in HP and its role for diagnosis is questionable. We analyzed the data of 152 HP patients for type of defect, lung volume, and DLCO. The present study is a retrospective analysis of 152 patients at one of the tertiary chest institutes in India. All diagnosed cases with at least spirometry were included. PFT findings were classified and graded as obstructive, restrictive, and mixed patterns. The correlation of PFT was calculated with disease duration and 6MWT distance. The majority were female [106 (70%)], with a mean age of 47.8 ± 12.3 years. Spirometry with lung volume data were available for 97% patients. PFT was abnormal in 118 (80%) cases. Among the patterns of abnormality, the most common type was restrictive (74%) followed by mixed (15%) and obstructive (11%) with the majority in the severe to very severe grade. The mean total lung capacity (TLC) and residual volume (RV) were reduced, with the grade more severe when the pattern of abnormality was restrictive while the RV/ TLC was higher suggestive of air tapping. DLCO data were available for 132 (87%) cases, with levels decreased in 67%. The severity of DLCO was highest when the pattern of abnormality was restrictive. One of the PFT parameters was abnormal in 137 (90%) cases, with isolated decreased DLCO levels seen in 16 (10%) cases. Forced vital capacity (FVC), TLC, and DLCO showed positive correlation with 6MWT distance (FVC r = .22, P = .02; TLC r = .28, P = .003; DLCO r = .30, P = .002). The PFT abnormality is seen in >80% of HP patients. All types of abnormality were seen, with the restrictive pattern being the most common. Isolated decreased DLCO levels were seen in 10% of cases. We advised to do full PFT for diagnosis and followup of HP.

GDF15 as a potential biomarker to distinguish fibrotic from non-fibrotic hypersensitivity pneumonitis

Hypersensitivity Pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) characterized by fibrotic HP (fHP) or non-fibrotic HP (non-fHP). Fibrosis is associated with poor prognosis, emphasizing the need for biomarkers to distinguish fHP from non-fHP. This study aimed to determine the plasma levels of GDF15 in HP patients and assess its association with lung function and phenotype classification. GDF15 levels were quantified by ELISA in HP (n = 64), idiopathic pulmonary fibrosis (n = 54), and healthy control (n = 128) groups. Clinical, demographic, and functional data were obtained from medical records. High-resolution chest CT scans were used to classify HP patients into fHP and non-fHP groups. In addition, receiver operating characteristic analysis was performed to determine the cut-off point, sensitivity, and specificity. Our results revealed significantly elevated GDF15 levels in fHP compared to non-fHP (2539 ± 821 pg/ml versus 1783 ± 801 pg/ml; p = 0.009). The estimated cut-off point for plasma GDF15 levels to distinguish fHP from non-fHP was 2193.4 pg/ml (AUC 0.75). These findings suggest that GDF15 may serve as a valuable biomarker for differentiating between fHP and non-fHP, potentially indicating its involvement in lung fibrosis development in HP.

Signs of Alveolar Collapse in Idiopathic Pulmonary Fibrosis, Hypersensitivity Pneumonitis and Systemic Sclerosis Revealed by Inspiration and Expiration Computed Tomography

Idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP) and systemic sclerosis (SSc) are among the most common entities that cause pulmonary fibrosis. Alveolar collapse with subsequent collapse induration of lung tissue is thought to contribute to the fibrotic transformation. The purpose of this study was to examine lung tissue in computed tomography (CT) of non-diseased appearance during expiration for signs of increased density suggesting collapsibility in fibrosing lung diseases. We further analyzed the diaphragmatic movements during the respiratory cycle to determine relationships between density differences and the apex–diaphragm diameter. Significant differences in attenuation changes between inspiration and expiration of unaffected lung parenchyma were detected between IPF and controls and between HP and controls for all lung lobes (p < 0.001). Only minor differences were found between SSc and controls. There was no clinically relevant difference between patients with IPF and those with HP. The measured absolute apex–diaphragm diameter in inspiration and expiration demonstrated a statistically significant difference between patients with IPF versus normal controls. However, the diaphragmatic excursions were not different between these groups. Compared to controls, CT lung density increases significantly more during expiration in the fibrotic lungs of IPF and HP patients. The observed increase in density might indicate the collapse of alveoli during expiration and may represent a common pathophysiologic feature of fibrosing lung diseases. The density changes and lung extensions do not have the same ratios across different diseases and controls.

Machine learning-based metabolism-related genes signature, single-cell RNA sequencing, and experimental validation in hypersensitivity pneumonitis.

Metabolism is involved in the pathogenesis of hypersensitivity pneumonitis. To identify diagnostic feature biomarkers based on metabolism-related genes (MRGs) and determine the correlation between MRGs and M2 macrophages in patients with hypersensitivity pneumonitis (HP). We retrieved the gene expression matrix from the Gene Expression Omnibus database. The differentially expressed MRGs (DE-MRGs) between healthy control (HC) and patients with HP were identified using the "DESeq2" R package. The "clusterProfiler" R package was used to perform "Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses" on DE-MRGs. We used machine learning algorithms for screening diagnostic feature biomarkers for HP. The "receiver operating characteristic curve" was used to evaluate diagnostic feature biomarkers' discriminating ability. Next, we used the "Cell-type Identification by Estimating Relative Subsets of RNA Transcripts" algorithm to determine the infiltration status of 22 types of immune cells in the HC and HP groups. Single-cell sequencing and qRT-PCR were used to validate the diagnostic feature biomarkers. Furthermore, the status of macrophage polarization in the peripheral blood of patients with HP was determined using flow cytometry. Finally, the correlation between the proportion of M2 macrophages in peripheral blood and the diagnostic biomarker expression profile in HP patients was determined using Spearman analysis. We identified a total of 311 DE-MRGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that DE-MRGs were primarily enriched in processes like steroid hormone biosynthesis, drug metabolism, retinol metabolism, etc. Finally, we identified NPR3, GPX3, and SULF1 as diagnostic feature biomarkers for HP using machine learning algorithms. The bioinformatic results were validated using the experimental results. The CIERSORT algorithm and flow cytometry showed a significant difference in the proportion of M2 macrophages in the HC and HP groups. The expression of SULF1 was positively correlated with the proportion of M2-type macrophages. In addition, a positive correlation was observed between SULF1 expression and M2 macrophage proportion. Finally, we identified NPR3, GPX3, and SULF1 as diagnostic feature biomarkers for HP. Further, a correlation between SULF1 and M2 macrophages was observed, providing a novel perspective for treating patients with HP and future studies.

Environmental Exposures, Characteristics, and Treatment Outcomes of Hypersensitivity Pneumonitis at a Rural Appalachian Academic Medical Center: A Cross-sectional Study

Purpose: Hypersensitivity pneumonitis (HP) is a form of interstitial lung disease (ILD) caused by inhalational exposure to an antigen. Little is known about the exposures, outcomes, and management of HP in rural Appalachian patients. Methods: A retrospective cross-sectional study was conducted from January 1, 2017, to June 30, 2022, at a tertiary academic medical center. Sixty-two patients were initially screened, and seven patients fulfilled the inclusion criteria. The primary outcome was the exposure leading to HP. Secondary outcomes included the disease stage at diagnosis, smoking rate, treatment modalities, ILD exacerbation rate, and mortality. Results: Birds and mold are the more common exposures attributed to HP (both n=2, 28.57%). Novel exposures to continuous positive airway pressure devices, vapor and/or fumes, and fiberglass were noted (each n=1, 14.28%). Three patients (42.85%) had fibrotic HP at presentation. Most patients were ever-smokers (n=4, 57.14%). All patients (n=7, 100%) received corticosteroids with a mean duration of use of 2.50 ± 0.65 months, and a mean dose of 37.14 ± 12.54 mg. One (14%) patient was compliant with antigen elimination. ILD exacerbation and mortality rate was high (both n=2, 28.57%). Conclusion: The exposures identified in rural Appalachian HP patients were similar to other rural and urban populations in the United States. Risk factors associated with poor outcomes, such as smoking, fibrotic HP subtype, and non-avoidance of antigen were higher in this cohort. The rate of ILD exacerbation and mortality were similarly higher. Larger studies are needed to investigate longitudinal trends of exposure, characteristics, and management of HP to improve outcomes in rural populations.

Evaluation of high-resolution computed tomography findings and associated factors in hypersensitivity pneumonitis

Background/Aim: Hypersensitivity pneumonitis (HP) is a lung disease from inhaling diverse environmental and occupational organic substances, such as fungi, bacteria, birds, and occasionally nonorganic materials. An immune response triggers this condition. A high-resolution chest computed tomography (HRCT) scan is typically performed as part of the initial diagnostic assessment. This study assesses HRCT findings in HP patients and examines associated factors between fibrotic and non-fibrotic patient groups. Methods: This retrospective cross-sectional study encompassed all HP patients monitored between 2010 and 2022. The analysis included data from 117 patients. HRCT findings from the patients were categorized based on fibrosis presence, leading to the division of patients into fibrotic and non-fibrotic groups. Comparative analyses were conducted between these groups. Results: Among the 117 subjects analyzed, 59 (50.4%) were male, and 58 (49.6%) were female. The mean age at diagnosis was 52.1 (13.6) years, ranging from 20 to 81. The non-fibrotic HP group comprised 70 (59.8%) patients, while the fibrotic HP group comprised 47 (40.2%). The most prevalent HRCT findings were ground-glass opacity (90.6%), mosaic attenuation (87.2%), and traction bronchiectasis (50.4%). Statistically significant disparities were observed between non-fibrotic and fibrotic HP groups in terms of HRCT findings: ground-glass opacity, irregular linear opacities, reticulation, traction bronchiectasis, honeycombing, and fibrosis (P=0.024, P<0.001). In contrast, the lymphocyte ratio in bronchoalveolar lavage fluid was 28.78 (16.2) in the non-fibrotic HP group and 14.66 (10.3) in the fibrotic HP group. The fibrotic HP group exhibited a statistically significant lower lymphocyte ratio in bronchoalveolar lavage fluid (P<0.001). Conclusion: HRCT findings are pivotal in HP diagnosis and classification. Computed tomography also assists in delineating the HP classification. This study identified ground-glass opacity and mosaic attenuation as the most prevalent HRCT findings in HP patients. Investigating the connection between fibrosis and prognosis is vital for determining patient outcomes, as fibrosis appears to be the principal determinant.

Transcriptome analysis for the screening of hub genes and potential drugs in hypersensitivity pneumonitis

Hypersensitivity pneumonitis (HP), an immune-mediated subtype of interstitial lung diseases (ILDs), is mediated by repetitive inhalation of certain antigens. Transcriptomic signatures, which provide insight into the genetic alterations associated with a disease, somehow remain obscure for HP. In this study, unique transcriptome fingerprints associated with the pathogenesis of HP were investigated using systems biology approach. Furthermore, the metabolic signatures identified in our earlier study, were correlated with the differentially expressed genes (DEGs) to explore the integrated pathways. Two datasets (GSE150910 and GSE19314) procured from the Gene Expression Omnibus repository were used to identify the DEGs of HP patients. The enriched biological processes, altered pathways and protein-protein interaction (PPI) network associated with the DEGs were determined. Based on topological algorithms, 12 hub genes were screened; among which chemokine (C-X-C motif) ligand 13 (CXCL13), CXCL9 and ribosomal protein large 36A (RPL36A) were identified as the top-ranked hub genes. The expression levels of these three candidate genes were experimentally validated in an HP patient cohort using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The findings indicated a trend similar to that of the bioinformatics observations. We integrated the metabolic signatures identified earlier with these hub genes and found glycolysis and phosphatidylinositol-3-kinase (PI3K/AKT) pathways to be impaired in these patients. Finally, the drug-gene interaction database DGIdb 4.0 indicated rituximab to be a promising drug for the management of HP. The present study is the first of its kind to combine bioinformatics and experimental data to identify and validate the genetic signatures and downstream pathways associated with HP. Our findings open up a new window to probe into the gene-metabolite crosstalk involved in the pathogenesis of HP and highlight promising therapeutic strategies.

The Presence of T Allele (rs35705950) of the MUC5B Gene Predicts Lower Baseline Forced Vital Capacity and Its Subsequent Decline in Patients with Hypersensitivity Pneumonitis.

Hypersensitivity pneumonitis (HP) is an exposure-related interstitial lung disease with two phenotypes-fibrotic and non-fibrotic. Genetic predisposition is an important factor in the disease pathogenesis and fibrosis development. Several genes are supposed to be associated with the fibrosing cascade in the lungs. One of the best-recognized and most prevalent is the common MUC5B gene promoter region polymorphism variant rs35705950. The aim of our study was to establish the frequency of the minor allele of the MUC5B gene in the population of patients with HP and to find the relationship between the MUC5B promoter region polymorphism and the development of lung fibrosis, the severity of the disease course, and the response to the treatment in patients with HP. Eighty-six consecutive patients with HP were tested for the genetic variant rs35705950 of the MUC-5B gene. Demographic, radiological, and functional parameters were collected. The relationship between the presence of the T allele and lung fibrosis, pulmonary function test parameters, and the treatment response were analyzed. The minor allele frequency in the study group was 17%, with the distribution of the genotypes GG in 69.8% of subjects and GT/TT in 30.2%. Patients with the GT/TT phenotype had significantly lower baseline forced vital capacity (FVC) and significantly more frequently had a decline in FVC with time. The prevalence of lung fibrosis in high-resolution computed tomography (HRCT) was not significantly increased in GT/TT variant carriers compared to GG ones. The patients with the T allele tended to respond worse to immunomodulatory treatment and more frequently received antifibrotic drugs. In conclusions: The frequency of MUC5B polymorphism in HP patients is high. The T allele may indicate a worse disease course, worse immunomodulatory treatment response, and earlier need for antifibrotic treatment.

Impact of radiographic honeycombing on transplant free survival and efficacy of immunosuppression in fibrotic hypersensitivity pneumonitis

BackgroundThe distinction between hypersensitivity pneumonitis (HP) and idiopathic pulmonary fibrosis (IPF) was thought to be important due to the difference in mortality between the conditions as well as the response to treatment. However, recent work suggests that the clinical diagnosis may matter less than certain radiographic features, namely usual interstitial pneumonia (UIP) pattern. The purpose of this study is to evaluate whether radiographic honeycombing is more predictive of transplant-free survival (TFS) than other clinical, radiographic, or histologic findings that distinguish HP from IPF in the current guidelines and to evaluate the impact of radiographic honeycombing on the efficacy of immunosuppression in fibrotic HP.MethodsWe retrospectively identified IPF and fibrotic HP patients evaluated between 2003 and 2019. Univariable and multivariable logistic regression was performed for patients with fibrotic HP and IPF to evaluate TFS. To assess the impact of treatment with immunosuppression on TFS in fibrotic HP, a cox proportional hazard model adjusted for known predictors of survival in HP including age, gender, and baseline pulmonary function testing results was constructed, and p-interaction for the presence of honeycombing on high resolution computed tomography and use of immunosuppression was calculated.ResultsOur cohort included 178 with IPF and 198 with fibrotic HP. In a multivariable analysis, the presence of honeycombing had a greater impact on the TFS than the diagnosis of HP vs. IPF. Among the criteria used in the HP diagnostic guidelines, only typical HP scan impacted survival in a multivariable model, while identification of antigen and surgical lung biopsy findings had no impact on survival. We identified a trend toward worse survival on immunosuppression in those with HP with radiographic honeycombing.ConclusionOur data suggests that honeycombing and baseline pulmonary function testing have a greater impact on TFS than the clinical diagnosis of IPF vs. fibrotic HP and that radiographic honeycombing is a predictor of poor TFS in fibrotic HP. We suggest that invasive diagnostic testing including surgical lung biopsy may not be useful in predicting mortality in HP patients with honeycombing and may potentially increase risk of immunosuppression.

Study of nasal mucosa histopathological changes in patients with hypersensitivity pneumonitis

Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops after inhalation of a variety antigens in susceptible individuals. The nasal mucosa is constantly exposed to these antigens that can irritate the respiratory mucosa. So, the purpose of this study was to study nasal histopathological changes in order to identify any shared pathological changes between the upper airways and the well-known pathological features of HP. 40 HP patients diagnosed at the Chest Department, Kasr Alainy hospital following ATS/JRS/ALAT guidelines were included. Patients were subjected to thorough history, high-resolution computed tomography, spirometry, cough evaluation test (CET), sinonasal outcome test-22 (SNOT-22), sinonasal examination and nasal mucosal biopsy by an otolaryngologist under visualization by a rigid nasal endoscope. The mean age of the patients was 46.2 ± 13.5 (85% were females and 15% were males). 90% of patients presented with cough and the mean CET was 17.15 ± 5.59.77.5% of patients suffered from sinonasal symptoms and the mean SNOT-22 was 12.18 ± 3.8. There was a significant correlation between the burden of sinonasal symptoms represented by the SNOT-22 and the severity of the cough represented by CET (r 0.40, p 0.01). 87.5% of HP patients had chronic inflammation of the nasal mucosa with predominant lymphocytic infiltration in 72.5% of patients. 77.5% of HP patients had a high burden of sinonasal symptoms which is positively associated with cough severity. 72.5% of patients had predominately lymphocytic infiltration of the nasal mucosa.Trial registration: retrospectively registered, registration number is NCT05723796, date of registration 13/02/2023.

Characteristics of a diagnostic bronchoscopy in hypersensitivity pneumonitis.

Bronchoalveolar 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. We 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. 88 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. Our 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.

New York Heart Association class and pulmonary artery pressure as prognostic factors of interstitial lung disease survival.

The aim of this study was to evaluate New York Heart Association (NYHA) class and systolic pulmonary artery pressure (sPAP) as survival predictors in major interstitial lung diseases (ILD) including idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and hypersensitivity pneumonitis (HP) and in other ILD like granulomatosis with polyangiitis (GPA). We analyzed survival, NYHA class, sPAP, and Octreoscan uptake index (UI) in 104 ILD patients (59 IPF, 19 NSIP, 10 HP and 16 GPA; median age 60.5 years) all referred to a single centre. Median survival was 68 months, with 1- and 2-year survival of 91% and 78%, respectively. Survival was lower among IPF and NSIP vs. HP and GPA patients (p=0.01). NYHA class 3-4 was more frequent among IPF (76.3%) vs. NSIP patients (31.6%; p<0.001). HP and GPA had NYHA class 1-2. NYHA class was negatively associated with survival (class 1=90.3 months vs. class 3=18.3 months and class 4=5.1 months; p=0.001). sPAP was >55 mmHg in 76.3% of patients with IPF and 35-55 mmHg in 63.2% of patients with NSIP. Patients with HP and GPA had sPAP < 55 mmHg. Among patients with IPF, NYHA and sPAP were negatively associated with survival (p<0.01) both showed a parallel trend. High-resolution computed tomography and survival were worse among IPF and NSIP vs. HP and GPA patients (p<0.001). Octreoscan UI was <10, 10-12, and >12 in IPF, NSIP, HP and GPA, respectively. Octreoscan UI was negatively associated with survival (p=0.002). NYHA class and sPAP are comparable ILD survival predictors. NYHA class is correlated with worse prognosis for IPF and NSIP vs. HP and GPA patients.

New 6-Minute-Walking Test Parameter-Distance/Desaturation Index (DDI) Correctly Diagnoses Short-Term Response to Immunomodulatory Therapy in Hypersensitivity Pneumonitis.

6MWT parameters (distance, initial saturation, final saturation, desaturation, distance-saturation product (DSP), and DDI) were analyzed at baseline and after 3 to 6 months of treatment with corticosteroids alone or in combination with azathioprine. 91 consecutive HP patients diagnosed and treated in a single pulmonary unit from 2005 to 2017 entered the study. There were 44 (48%) males and 52 (57%) patients with fibrotic HP (fHP). Sixty-three patients (69%) responded to treatment (responders) and 28 (31%) did not respond (non-responders). In the responders group, all parameters assessed during 6MWT significantly improved, whereas in non-responders, they worsened. Medians (95% CI) of best indices were post-treatment DDI/baseline DDI-1.67 (1.85-3.63) in responders versus 0.88 (0.7-1.73) in non-responders (p = 0.0001) and change in walking distance-51 m (36-72 m) in responders, versus 10.5 m (-61.2-27.9) in non-responders (p = 0.0056). The area under the curve (AUC) of receiver operating characteristics (ROC) for post-treatment DDI/baseline DDI was 0.74 and the optimal cut-off was 1.075, with 71% of specificity and 71% of sensitivity. 6MWT may be used as a tool to assess and monitor the response to immunomodulatory therapy in HP patients, especially if indices incorporating both distance and desaturation are used. Based on the present study results, we recommend 6MWD and DDI use, in addition to FVC and TL,co, to monitor treatment efficacy in patients with interstitial lung diseases.

Role of circulating serum YKL-40 level in assessment of severity in hypersensitivity pneumonitis patients

BACKGROUND: Hypersensitivity pneumonitis (HP) is a diffuse parenchymal lung disease characterized by immune-mediated inflammation of lung parenchyma triggered by exposure to a wide variety of inhaled antigens. YKL-40 plays a fundamental role in protecting against pathogens, antigen-induced and oxidant-induced injury responses, inflammation, and tissue repair and remodeling. This is achieved by regulating many biological processes.

Hipersensitivite pnömonisi hastalarında sistemik kortikosteroid tedavi yanıtı: bir tek merkez deneyimi

Aim: Hypersensitivity pneumonitis (HP) is defined as an inflammatory and/or fibrotic immune reaction provoked by an inhalational exposure in susceptible individuals. Initial management of HP patients includes remediation of exposure and treatment with immunosuppressive agents. In this study we aimed to define clinical features and treatment modalities and to evaluate response to corticosteroids in HP patients followed in a single tertiary care setting. Materials and Methods: The patients with HP diagnosis followed between 1 January 2019 and 31 December 2020 were included in this retrospective study. Firstly, the candidate factors related with treatment response were evaluated by univariate analysis and then the possible factors with p values below 0.15 were evaluated by multiple linear regression model to identify independent predictors of systemic corticosteroid response. Results: The study population consisted of 50 HP patients and 20 of them (40%) had fibrotic HP. Forty-one (82.0%) patients were followed with a medical treatment for longer than 3 months. Within follow-up period 15 (36.5%) patients didn’t show clinical or radiological response to systemic corticosteroids. Patients without treatment response were presented as fibrotic HP (66.6% vs 26%, p=0.02), had radiological features of fibrosis (86.6% vs 30.7%, p=0.002) and had loss of pulmonary functions (60.0% vs 34.6%, p=0.03) more frequently. Uni-variable analysis revealed that radiological features of fibrosis (OR: 0.07 [95%CI: 0.01-0.42], p=0.003) and mosaic attenuation (OR: 7.0 [95%CI: 0.30-10.07], p=0.08) in HRCT related with corticosteroid treatment response. Conclusion: Our study suggests radiological features of fibrosis relate with worse clinical and radiological response to corticosteroid treatment. Prospective clinical trials are needed to clarify the role of immunosuppressive therapy in HP patients.

Impact of antigen avoidance test for fibrotic hypersensitivity pneumonitis in stable phase.

The antigen avoidance has been used in the diagnosis and treatment of hypersensitivity pneumonitis (HP); however, its usefulness in stable fibrotic HP is controversial. To investigate the usefulness of the antigen avoidance test in patients with fibrotic HP in stable phase. The antigen avoidance test was conducted during a 2-week hospitalization comparing clinical parameters at admission and before discharge. A retrospective review of patients who underwent surgical lung biopsy or transbronchial lung cryobiopsy, who were diagnosed with fibrotic HP by multi-disciplinary discussion, and whose disease progression was stable for more than two months before the antigen avoidance test was done. Between 2016 and 2021, 40 patients met the criteria, and 17 (43%) patients had a positive antigen avoidance test. The patients with positive in the antigen avoidance test had significantly greater annual forced vital capacity (FVC) decline than those with negative before the test (- 6.5% vs. - 0.3%, p = 0.045). The patients with positive antigen avoidance test had less annual FVC decline than those with negative in the year following the test (0.8% vs. - 5.0%, p = 0.048). The differences in annual improvement were found for serum Krebs von den Lungen-6 between the positive and negative patients in the year following the test (- 27% vs. - 5%, p = 0.049). In multivariate Cox hazard regression analysis, a negative result of the antigen avoidance test was a risk factor for death or acute exacerbation of fibrotic HP (HR = 0.26 [95% CI: 0.07-0.90], p = 0.034). In fibrotic HP patients in stable phase, the antigen avoidance test under a 2-week hospitalization was valuable in predicting prognosis.