Making Sense of Bronchoalveolar Lavage Lymphocytosis in Fibrotic Interstitial Lung Disease.
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ABSTRACT:
SUBMITTER: Ryerson CJ
PROVIDER: S-EPMC7640718 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease.To evaluate whether lavage cellularity identifies distinct subsets of disease and/or predicts cyclophosphamide responsiveness.Patients underwent baseline lavage and/or high-resolution computed tomography as part of a randomized placebo-controlled trial of cyclophosphamide versus placebo (Scleroderma Lung Study) to determine the effect of therapy on forced vital capacity. Patients with 3% or greater polymorphonuclear and/or 2% or greater eosinophilic leukocytes on lavage and/or ground-glass opacification on computed tomography were eligible for enrollment.Lavage was performed in 201 individuals, including 141 of the 158 randomized patients. Abnormal cellularity was present in 101 of these cases (71.6%) and defined a population with a higher percentage of men (P = 0.04), more severe lung function, including a worse forced vital capacity (P = 0.003), worse total lung capacity (P = 0.005) and diffusing capacity of the lung for carbon monoxide (P = 0.004), more extensive ground-glass opacity (P = 0.005), and more extensive fibrosis in the right middle lobe (P = 0.005). Despite these relationships, the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year (P = not significant).The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response. Clinical trial registered with www.clinicaltrials.gov (NCT 000004563).
| S-EPMC2176114 | biostudies-other
Project description:BackgroundThe utility of bronchoalveolar lavage (BAL) in the evaluation of systemic sclerosis-associated interstitial lung disease (SSc-ILD) remains controversial. Fractional analysis of BAL (FBAL) is a technique that can analyze small airways and alveolar compartments separately and has proven informative in other ILDs. The aim of this study was to explore FBAL characteristics across the spectrum of SSc-ILD severity.MethodsWe retrospectively reviewed patients with SSc-ILD who underwent bronchoscopy with FBAL using three 50 mL aliquots of saline solution. These aliquots were analyzed separately for differential cell composition (FBAL-1, -2, and -3). We compared the FBAL cell composition to the progression of ILD and end-stages of ILD using Cox proportional hazards models.ResultsSixty-eight patients with SSc-ILD were enrolled in this study. The percentage of neutrophils and eosinophils was lower in FBAL-3 compared to FBAL-1. In contrast, the percentage of macrophages and lymphocytes was higher in FBAL-3. Neutrophils in FBAL-2, -3, and the estimated total FBAL cell fraction (FBAL-total) were negatively correlated with the forced vital capacity % predicted (r=-0.420, -0.362, -0.409, respectively). Although FBAL-total was not linked to the progression and end-stage of ILD, a high percentage of neutrophils in FBAL-3 was significantly associated with the development of end-stage ILD (HR 1.093, 95% CI: 1.003-1.190).ConclusionsA higher percentage of neutrophils in FBAL-3 is correlated with development of end-stage ILD in SSc-ILD as well as mortality.
| S-EPMC8339759 | biostudies-literature
Project description:BackgroundIdiopathic non-specific interstitial pneumonia (iNSIP), idiopathic pleuroparenchymal fibroelastosis (iPPFE), and unclassifiable idiopathic interstitial pneumonia (IIP) are IIPs with chronic fibrotic phenotypes, and unlike idiopathic pulmonary fibrosis, they have often been treated with anti-inflammatory drugs, including corticosteroids and immunosuppressants. However, the impact of bronchoalveolar lavage (BAL) lymphocytosis on the effects of anti-inflammatory therapy has never been evaluated. This study aimed to elucidate whether BAL lymphocytosis can be used to predict the efficacy of anti-inflammatory drugs for iNSIP, iPPFE, and unclassifiable IIP.MethodsJapanese patients diagnosed with iNSIP, iPPFE, and unclassifiable IIP by multidisciplinary discussion were identified using the nationwide registry. Eligible patients were stratified into four groups with and without BAL lymphocytosis and anti-inflammatory therapy to compare overall survival (OS) and changes in lung function. BAL lymphocytosis was defined as a lymphocyte differential count > 15%, and the cut-off was corroborated by survival classification and regression tree analysis.ResultsOverall, 186 patients (37 iNSIP, 16 iPPFE, and 133 unclassifiable IIP) were analyzed. Limited to patients treated with anti-inflammatory drugs (n = 123), patients with BAL lymphocytosis had a better prognosis [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.11-0.63; P = 0.003], higher slope of forced vital capacity (FVC) % predicted for 2 years, and longer OS (log-rank test, P = 0.012) than those without BAL lymphocytosis. On multivariate analysis, BAL lymphocytosis (HR 0.31; 95% CI 0.13-0.75; P = 0.009) was a prognostic factor for OS, along with age and FVC % predicted. Conversely, for patients managed without anti-inflammatory therapy (n = 63), the presence or absence of BAL lymphocytosis had no prognostic value.ConclusionsBAL lymphocytosis is associated with good outcomes in patients treated with anti-inflammatory drugs, but has no prognostic value when anti-inflammatory drugs are not used. BAL lymphocytosis may provide a predictive biomarker for identifying patients with iNSIP, iPPFE and unclassifiable IIP who are likely to benefit from anti-inflammatory drugs.
| S-EPMC8059166 | biostudies-literature
Project description:BackgroundThe pathogenesis of connective tissue disease-associated interstitial lung disease (CTD-ILD) is unclear. This study aims to identify differentially expressed proteins (DEPs) in CTD-ILD to determine the potential role of these DEPs that may play in the pathogenesis of CTD-ILD and to offer potential therapeutic targets.MethodsBronchoalveolar lavage fluid (BALF) samples were collected from four patients with CTD-ILD and four patients without CTD-ILD. Label-free mass spectrometry-based relative quantification was used to identify the DEPs. Bioinformatics were used to determine the potential biological processes and signaling pathways associated with these DEPs.ResultsWe found 65 upregulated DEPs including SFTPD, CADM1, ACSL4, TSTD1, CD163, LUM, SIGLEC1, CPB2, TGFBI and HGD, and 67 downregulated DEPs including SGSH, WIPF1, SIL1, RAB20, OAS3, GMPR2, PLBD1, DNAJC3, RNASET2 and OAS2. The results of GO functional annotation for the DEPs showed that the DEPS were mainly enriched in the binding, cellular anatomical entity, cellular processes, and biological regulation GO terms. The results of KEGG analyses showed that the pathways most annotated with the DEPs were complement and coagulation cascades, metabolic pathways, pathways in cancer, and PPAR signaling pathway. COG analyses further informed the functions associated with these DEPs, with most focused on signal transduction mechanisms; posttranslational modification, protein turnover, chaperones; intracellular trafficking, secretion, and vesicular transport; amino acid transport and metabolism; and lipid transport and metabolism.ConclusionsDEPs identified between patients with vs. without CTD-ILD may play important roles in the development of CTD-ILD and are potential new biomarkers for early diagnosis of CTD-ILD.
| S-EPMC9102639 | biostudies-literature
Project description:Interstitial lung diseases (ILD) on the whole have variable prognoses, but there are those which manifest with fibrosis and are characterized by disease progression. Chief among these is idiopathic pulmonary fibrosis, but other ILDs, including autoimmune ILD and chronic hypersensitivity pneumonitis, may have a progressive fibrotic phenotype also. A usual interstitial pneumonia pattern of lung involvement is a prominent risk factor for such a course, suggesting shared fibrotic pathways that may be targeted by antifibrotic therapies. This brief review describes ILDs that are most commonly fibrotic, shared risk factors for development of PF-ILD, and evidence for antifibrotic use in their management.
| S-EPMC8965041 | biostudies-literature
Project description:Bronchoalveolar lavage (BAL) plays a role in the diagnosis of diffuse parenchymal lung diseases (DPLD); however, poor BAL fluid (BALF) recovery results in low diagnostic reliability. BAL is relatively safe, but its indications should be carefully considered in patients with risks. Therefore, estimating the likelihood of recovery failure is helpful in clinical practice. This study aimed to clarify predictors of BALF recovery failure and to develop its simple-to-use prediction models. We detected the predictors applying a logistic regression model on clinical, physiological, and radiological data from 401 patients with DPLD (derivation cohort). The discrimination performance of the prediction models using these factors was evaluated by the c-index. In the derivation cohort, being a man, the forced expiratory volume in one second/forced vital capacity, and a BAL target site other than right middle lobe or left lingula were independent predictors. The c-indices of models 1 and 2 that we developed were 0.707 and 0.689, respectively. In a separate cohort of 234 patients (validation cohort), the c-indices of the models were 0.689 and 0.670, respectively. In conclusion, we developed and successfully validated simple-to-use prediction models useful for pulmonologists considering BAL indications or target sites, based on independent predictors for BALF recovery failure.
| S-EPMC7814131 | biostudies-literature
Project description:Background and Objectives: Interstitial lung diseases have always been an issue for pulmonary and rheumatology physicians. Computed tomography scans with a high-resolution protocol and bronchoalveolar lavage have been used along with biochemical blood tests to reach a diagnosis. Materials and Methods: We included 80 patients in total. First, all patients had their diagnosis with computed tomography of the thorax, serological/ immunological blood tests and bronchoalveolar lavage. However; after 3 months, all were divided into 2 groups: those who had bronchoalveolar lavage again and those who had cryobiopsy instead of bronchoalveolar lavage (40/40). Positron emission-computed tomography was also performed upon the first and second diagnosis. The patients' follow-up was 4 years from diagnosis. Results: Patients suffered most from chronic obstructive pulmonary disease (56, 70%), while lung cancer was rarely encountered in the sample (7, 9.75%). Age distribution ranged between 53 and 68 years with a mean value of 60 years. The computed tomography findings revealed 25 patients with typical diagnosis (35.2%), 17 with interstitial pulmonary fibrosis (23.9%) and 11 with probable diagnosis (11%). The cryobiopsy technique led to a new diagnosis in 28 patients (35% of the total sample). Patients who had a new diagnosis with cryobiopsy had a mean survival time of 710 days (<1460). Positron emission-computed tomography SUV uptake was positively associated with the cryobiopsy technique/new disease diagnosis and improved all respiratory functions. Discussion: Positron emission-computed tomography is a tool that can be used along with respiratory functions for disease evaluation. Conclusions: Cryobiopsy is a safe tool for patients with interstitial lung disease and can assist in the diagnosis of interstitial lung diseases. The survival of patients was increased in the cryobiopsy group versus only bronchoalveolar lavage for disease diagnosis.
| S-EPMC10144839 | biostudies-literature
Project description:Fibrotic interstitial lung diseases (ILDs) have a high mortality rate with an unpredictable disease course and clinical features that frequently overlap. Recent data indicate important roles for genomics in the mechanisms underlying susceptibility and progression of pulmonary fibrosis. The impact of these genomic markers on pharmacotherapy and their contribution to outcomes is increasingly recognized. Interstitial lung abnormalities, frequently considered representative of early ILD, have been consistently associated with the MUC5B promoter polymorphism, a common gene variant. Other rare gene variant mutations, including TERT, TERC, SFTPC, and DKC1, may be present in patients with familial interstitial pneumonia and are frequently associated with a usual interstitial pneumonia pattern of fibrosis. The minor allele of the MUC5B rs35705950 genotype is prevalent in several sporadic forms of ILD, including idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. Gene mutations that characterize familial pulmonary fibrosis may be present in patients with connective tissue disease-related ILD, such as rheumatoid arthritis-ILD. Additionally, shorter telomere lengths and mutations in telomere biology-related genes have been demonstrated in both familial and sporadic ILD, with significant implications for disease progression, lung function, and survival. An improved understanding of the impact of genetic and genomic risk factors on disease progression would better guide personalized therapeutic choices in persons with fibrotic ILD.
| S-EPMC6533453 | biostudies-literature
Project description:BackgroundDehydroepiandrosterone (DHEA) is a precursor sex hormone with antifibrotic properties. The aims of this study were to investigate antifibrotic mechanisms of DHEA, and to determine the relationship between DHEA-sulfate (DHEAS) plasma levels, disease severity and survival in patients with fibrotic interstitial lung diseases (ILDs).MethodsHuman precision cut lung slices (PCLS) and normal human lung fibroblasts were treated with DHEA and/or transforming growth factor (TGF)-β1 before analysis of pro-fibrotic genes and signal proteins. Cell proliferation, cytotoxicity, cell cycle and glucose-6-phosphate dehydrogenase (G6PD) activity were assessed. DHEAS plasma levels were correlated with pulmonary function, the composite physiologic index (CPI), and time to death or lung transplantation in a derivation cohort of 31 men with idiopathic pulmonary fibrosis (IPF) and in an independent validation cohort of 238 men and women with fibrotic ILDs.ResultsDHEA decreased the expression of pro-fibrotic markers in-vitro and ex-vivo. There was no cytotoxic effect for the applied concentrations, but DHEA interfered in proliferation by modulating the cell cycle through reduction of G6PD activity. In men with IPF (derivation cohort) DHEAS plasma levels in the lowest quartile were associated with poor lung function and higher CPI (adjusted OR 1.15 [95% CI 1.03-1.38], p = 0.04), which was confirmed in the fibrotic ILD validation cohort (adjusted OR 1.03 [95% CI 1.00-1.06], p = 0.01). In both cohorts the risk of early mortality was higher in patients with low DHEAS levels, after accounting for potential confounding by age in men with IPF (HR 3.84, 95% CI 1.25-11.7, p = 0.02), and for age, sex, IPF diagnosis and prednisone treatment in men and women with fibrotic ILDs (HR 3.17, 95% CI 1.35-7.44, p = 0.008).ConclusionsDHEA reduces lung fibrosis and cell proliferation by inducing cell cycle arrest and inhibition of G6PD activity. The association between low DHEAS levels and disease severity suggests a potential prognostic and therapeutic role of DHEAS in fibrotic ILD.
| S-EPMC9178848 | biostudies-literature
Project description:BackgroundAbout 20% of patients with common variable immunodeficiency (CVID) suffer from interstitial lung disease (ILD) as part of a systemic immune dysregulation. Current understanding suggests a role of B cells in the pathogenesis based on histology and increased levels of BAFF and IgM associated with active disease corroborated by several reports which demonstrate the successful use of rituximab in CVID-ILD. It is debated whether histological confirmation by biopsy or even video-assisted thoracoscopy is required and currently not investigated whether less invasive methods like a bronchoalveolar lavage (BAL) might provide an informative diagnostic tool.ObjectiveTo gain insight into potential immune mechanisms underlying granulomatous and lymphocytic interstitial lung disease (GLILD) and to define biomarkers for progressive ILD by characterizing the phenotype of B- and T-cell populations and cytokine profiles in BAL fluid (BALF) of CVID-ILD compared to sarcoidosis patients and healthy donors (HD).MethodsSixty-four CVID, six sarcoidosis, and 25 HD BALF samples were analyzed by flow cytometric profiling of B- and T-cells and for cytokines by ELISA and Multiplexing LASER Bead technology.ResultsBoth sarcoidosis and CVID-ILD are characterized by a predominantly T-cell mediated lymphocytosis in the BALF. There is an increase in T follicular helper (TFH)-like memory and decrease of regulatory T cells in CVID-ILD BALF. This TFH-like cell subset is clearly skewed toward TH1 cells in CVID-ILD. In contrast to sarcoidosis, CVID-ILD BALF contains a higher percentage of B cells comprising mostly CD21low B cells, but less class-switched memory B cells. BALF analysis showed increased levels of APRIL, CXCL10, and IL-17.ConclusionUnlike in sarcoidosis, B cells are expanded in BALF of CVID-ILD patients. This is associated with an expansion of TFH- and TPH-like cells and an increase in APRIL potentially supporting B-cell survival and differentiation and proinflammatory cytokines reflecting not only the previously described TH1 profile seen in CVID patients with secondary immune dysregulation. Thus, the analysis of BALF might be of diagnostic value not only in the diagnosis of CVID-ILD, but also in the evaluation of the activity of the disease and in determining potential treatment targets confirming the prominent role of B-cell targeted strategies.
| S-EPMC7892466 | biostudies-literature