Pulmonary Biomarkers Research Articles

Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation.

There is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The semi-synthetic polysaccharide, Pentosan polysulfate sodium (PPS), an inhibitor of NF-kB activation, was investigated for its systemic and local anti-inflammatory effects in a mouse model of influenza virus A/PR8/1934 (PR8 strain) mediated infection. Immunocompetent C57BL/6J mice were infected intranasally with a sublethal dose of PR8 and treated subcutaneously with 3 or 6 mg/kg PPS or vehicle. Disease was monitored and tissues were collected at the acute (8 days post-infection; dpi) or post-acute (21 dpi) phase of disease to assess the effect of PPS on PR8-induced pathology. In the acute phase of PR8 infection, PPS treatment was associated with a reduction in weight loss and improvement in oxygen saturation when compared to vehicle-treated mice. Associated with these clinical improvements, PPS treatment showed a significant retention in the numbers of protective SiglecF+ resident alveolar macrophages, despite uneventful changes in pulmonary leukocyte infiltrates assessed by flow cytometry. PPS treatment in PR8- infected mice showed significant reductions systemically but not locally of the inflammatory molecules, IL-6, IFN-g, TNF-a, IL-12p70 and CCL2. In the post-acute phase of infection, PPS demonstrated a reduction in the pulmonary fibrotic biomarkers, sICAM-1 and complement factor C5b9. The systemic and local anti-inflammatory actions of PPS may regulate acute and post-acute pulmonary inflammation and tissue remodeling mediated by PR8 infection, which warrants further investigation.

An explainable machine learning-driven proposal of pulmonary fibrosis biomarkers

Pulmonary fibrosing diseases are in the very epicenter of biomedical research both due to their increasing prevalence and their association with SARS-CoV-2 infections. Research of idiopathic pulmonary fibrosis, the most lethal among the interstitial lung diseases, is in need for new biomarkers and potential disease targets, a goal that could be accelerated using machine learning techniques. In this study, we have used Shapley values to explain the decisions made by an ensemble learning model trained to classify samples to an either pulmonary fibrosis or steady state based on the expression values of deregulated genes. This process resulted in a full and a laconic set of features capable of separating phenotypes to an at least equal degree as previously published marker sets. Indicatively, a maximum increase of 6% in specificity and 5% in Mathew’s correlation coefficient was achieved. Evaluation with an additional independent dataset showed our feature set having a greater generalization potential than the rest. Ultimately, the proposed gene lists are expected not only to serve as new sets of diagnostic marker elements, but also as a target pool for future research initiatives.

Protective effect of rivastigmine against lung injury in acute pancreatitis model in rats via Hsp 70/IL6/ NF-κB signaling cascade.

Acute lung injury (ALI) that develops as a result of AP can progress to acute respiratory distress syndrome. Some hypotheses are proposed to explain the pathophysiology of AP and its related pulmonary hazards. This experiment aimed to evaluate the mitigating action of rivastigmine (Riva) in lung injury that occurs on the top of acute pancreatitis (AP) induced in rats. Thirty-two male Wister rats were randomized to one of four groups: control, Riva-treated, acute pancreatitis (AP), and acute pancreatitis treated by Riva. Serum amylase and lipase levels were assessed. Pulmonary oxidative stress and inflammatory indicators were estimated. A pancreatic and pulmonary histopathological examination, as well as an immunohistochemical study of HSP70, was carried out. Riva significantly attenuated the L-arginine-related lung injury that was characterized by increased pulmonary inflammatory biomarkers (interleukin-6 [IL-6]), nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), increased pulmonary oxidative markers (total nitrite/nitrate [NOx]), MDA, decreased total antioxidant capacity (TAC), and reduced glutathione level (GSH)) with increased caspase-3 expression. Therefore, Riva retains potent ameliorative effects against lung injury that occur on the top of AP by relieving oxidative stress, inflammation, and apoptosis via HSP70/IL6/NF-κB signaling.

Detection of chronic obstructive pulmonary disease biomarkers using ROC-analysis

Aim. To identify key diagnostic criteria for chronic obstructive pulmonary disease (COPD).Materials and methods. We examined 112 patients with mild, moderate and severe COPD and 32 relatively healthy volunteers with no disturbances in the lung function. The level of IL-4, IL-6, IL-10, IL-17A, TNF-α, IFN-γ, TGF-β1 and CD4+CD126+ cells was determined by means of flow cytometry method. Prooxidant and antioxidant markers of oxidative stress 8-OHdeoxyguanosine, protein carbonyl, glutathione, glutathione reductase, glutathione peroxidase, thioredoxin-1, and thioredoxin reductase-1 were assessed by enzyme immunoassay.Results. The presence of high-ranking correlations of the proinflammatory link of immunity and components of the prooxidant system was revealed, which indicates the presence of systemic alterative processes in patients with COPD. Based on ROC-analysis, key biomarkers were identified in patients with stable COPD: 8-OH-deoxyguanosine, CD4+CD126+ cells, IL-17, and thioredoxin, and their threshold levels were established.Conclusion. The recommended diagnostic criteria will optimize the therapeutic strategies for COPD.

Taurine mitigates the development of pulmonary inflammation, oxidative stress, and histopathological alterations in a rat model of bile duct ligation.

Lung injury is a significant complication associated with cholestasis/cirrhosis. This problem significantly increases the risk of cirrhosis-related morbidity and mortality. Hence, finding effective therapeutic options in this field has significant clinical value. Severe inflammation and oxidative stress are involved in the mechanism of cirrhosis-induced lung injury. Taurine (TAU) is an abundant amino acid with substantial anti-inflammatory and antioxidative properties. The current study was designed to evaluate the role of TAU in cholestasis-related lung injury. For this purpose, bile duct ligated (BDL) rats were treated with TAU (0.5 and 1% w: v in drinking water). Significant increases in the broncho-alveolar lavage fluid (BALF) level of inflammatory cells (lymphocytes, neutrophils, basophils, monocytes, and eosinophils), increased IgG, and TNF-α were detected in the BDL animals (14 and 28days after the BDL surgery). Alveolar congestion, hemorrhage, and fibrosis were the dominant pulmonary histopathological changes in the BDL group. Significant increases in the pulmonary tissue biomarkers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, increased oxidized glutathione levels, and decreased reduced glutathione, were also detected in the BDL rats. Moreover, significant myeloperoxidase activity and nitric oxide levels were seen in the lung of BDL rats. It was found that TAU significantly blunted inflammation, alleviated oxidative stress, and mitigated lung histopathological changes in BDL animals. These data suggest TAU as a potential protective agent against cholestasis/cirrhosis-related lung injury.

Combined resistance and aerobic training improves lung function and mechanics and fibrotic biomarkers in overweight and obese women.

Background: Obesity impairs lung function and mechanics and leads to low-grade inflammation, but the effects of combined physical exercise (CPE) on that are unknown. Methods: We investigated the effects of 12 weeks of combined physical exercise (aerobic + resistance training), in non-obese (n = 12), overweight (n = 17), and obese grade I (n = 11) women. Lung function and lung mechanics were evaluated. The systemic immune response was evaluated by whole blood analysis and biomarker measurements, while pulmonary fibrotic biomarkers were evaluated in the breath condensate. Result: CPE improved forced vital capacity (FVC) % (p < 0.001) and peak expiratory flow (PEF) % (p < 0.0003) in the obese group; resistance of the respiratory system (R5Hz) in non-obese (p < 0.0099), overweight (p < 0.0005), and obese (p < 0.0001) groups; resistance of proximal airways (R20Hz) in non-obese (p < 0.01), overweight (p < 0.0009), and obese (p < 0.0001) groups; resistance of distal airways (R5Hz–R20Hz) in non-obese (p < 0.01), overweight (p < 0.0012), and obese (p < 0.0001) groups; reactance of the respiratory system (X5Hz) in non-obese (p < 0.01), overweight (p < 0.0006), and obese (p < 0.0005) groups; impedance of the respiratory system (Z5Hz) in non-obese (p < 0.0099), overweight (p < 0.0005), and obese (p < 0.0001) groups; central resistance (RCentral) in non-obese (p < 0.01), overweight (p < 0.001), and obese (p < 0.0003) groups; and the peripheral resistance (RPeripheral) in non-obese (p < 0.03), overweight (p < 0.001), and obese (p < 0.0002) groups. CPE reduced the pro-fibrotic IGF-1 levels in BC in overweight (p < 0.0094) and obese groups (p < 0.0001) and increased anti-fibrotic Klotho levels in BC in obese (p < 0.0001) groups, and reduced levels of exhaled nitric oxide in overweight (p < 0.03) and obese (p < 0.0001) groups. Conclusion: CPE improves lung function, mechanics, and pulmonary immune response in overweight and obese grade I women by increasing anti-fibrotic protein Klotho and reducing pro-fibrotic IGF-1.

Exploring Idiopathic Pulmonary Fibrosis Biomarker by Simultaneous Two-Photon Fluorescence Imaging of Cysteine and Peroxynitrite.

Idiopathic pulmonary fibrosis (IPF) has been characterized as a chronic inflammatory disease that leads to irreversible damage to pulmonary function. However, there is no specific IPF biomarker that can be used to distinguish IPF and not pneumonia. Endoplasmic reticulum (ER) stress is prominent in IPF. To search for a specific biomarker of IPF, we developed two ER-targeting two-photon (TP) fluorescent probes, TPER-ONOO and TPER-Cys, for peroxynitrite (ONOO-) and cysteine (Cys) imaging, respectively. A significant increase in Cys levels in the lungs was discovered only in mice with IPF, which implied that Cys might be an IPF biomarker candidate. Furthermore, we uncovered the mechanism of glutathione (GSH) deficiency in IPF, which was not due to Cys shortage but instead was attributable to impaired glutamate cysteine ligase and glutathione synthetase activities via ONOO--induced post-transcriptional modification. This work has potential to provide a new method for IPF early diagnosis and drug efficacy evaluation.

Recent Advances in Molecular Diagnosis of Pulmonary Fibrosis for Precision Medicine.

Pulmonary fibrosis is a serious, progressive lung disease characterized by scarring and stiffening lung tissues, affecting the respiratory system and leading to organ failure. It is a complex disease consisting of alveolar damage, chronic inflammation, and a varying degree of lung fibrosis. Significant challenges with pulmonary fibrosis include the lack of effective means to diagnose the disease at early stages, identify patients at higher risks of progress, and assess disease progression and treatment response. Precision medicine powered by accurate molecular profiling and phenotyping could significantly improve our understanding of the disease's heterogeneity, potential biomarkers for diagnosis and prognosis, and molecular targets for treatment development. This Review discusses various translational model systems, including organoids and lung-on-a-chip systems, biomarkers in single cells and extracellular vesicles, and functional pharmacodynamic markers. We also highlight emerging sensing technologies for molecular characterization of pulmonary fibrosis and biomarker detection.

Quantification of lung function on CT images based on pulmonary radiomic filtering.

To develop a radiomics filtering technique for characterizing spatial-encoded regional pulmonary ventilation information on lung computed tomography (CT). The lung volume was segmented on 46 CT images, and a 3D sliding window kernel was implemented across the lung volume to capture the spatial-encoded image information. Fifty-three radiomic features were extracted within the kernel, resulting in a fourth-order tensor object. As such, each voxel coordinate of the original lung was represented as a 53-dimensional feature vector, such that radiomic features could be viewed as feature maps within the lungs. To test the technique as a potential pulmonary ventilation biomarker, the radiomic feature maps were compared to paired functional images (Galligas PET or DTPA-SPECT) based on the Spearman correlation (ρ) analysis. The radiomic feature maps GLRLM-based Run-Length Non-Uniformity and GLCOM-based Sum Average are found to be highly correlated with the functional imaging. The achieved ρ (median [range]) for the two features are 0.46 [0.05, 0.67] and 0.45 [0.21, 0.65] across 46 patients and 2 functional imaging modalities, respectively. The results provide evidence that local regions of sparsely encoded heterogeneous lung parenchyma on CT are associated with diminished radiotracer uptake and measured lung ventilation defects on PET/SPECT imaging. These findings demonstrate the potential of radiomics to serve as a complementary tool to the current lung quantification techniques and provide hypothesis-generating data for future studies.

Determinants of asthma control and exacerbations in moderate to severe asthma

Determinants of asthma control and exacerbations in moderate to severe asthma

Pulmonary tuberculosis Biomarker discovery in the quest for new therapies

Pulmonary tuberculosis Biomarker discovery in the quest for new therapies

General anaesthesia with double-lumen intubation compared to opioid-sparing strategies with laryngeal mask for thoracoscopic surgery: A randomised trial

BackgroundGeneral anaesthesia for thoracoscopic lung surgery can be performed with the opioid-sparing strategies without intubation and may reduce the risk of glottic injury and enhance recovery after surgery. We therefore tested the primary hypothesis that avoiding intubation reduces glottic injury. MethodsAdults having elective thoracoscopic lung resections were randomised to: (1) intubated group: routine general anaesthesia with a double-lumen tube intubation; or, (2) non-intubated group: a bundle of opioid-sparing strategies, which included paravertebral blocks and total intravenous anaesthesia with minimal remifentanil infusion from 0.05 to 1.0 ng/mL (avoid sufentanil unless the respiratory rate exceeds 25/min or the systolic blood pressure exceeds 30% of the baseline value), no muscle relaxation, and spontaneous ventilation through a laryngeal mask. The primary outcome was glottal injury as determined by transnasal bronchoscopy one hour after removal of the laryngeal mask or double-lumen tube. ResultsTwo hundred seventeen patients were assessed for the primary outcome. Sufentanil use was reduced 96% and remifentanil was reduced 40% in non-intubated opioid-sparing patients. The incidence of glottal injury was 9% (10/109) in the non-intubated vs. 37% (40/108) in the intubated patients (RR: 0.25; 95%CI: 0.13–0.47, P < 0.001). The non-intubated group also had less postoperative sore throat (8% vs. 39%; P < 0.001) and hoarseness (3% vs. 19%; P < 0.001). Postoperative pulmonary complications and lung injury biomarkers did not differ between the groups. Compared to the intubated group, the non-intubated group had less postoperative pain, faster recovery, and improved quality-of-life scores. ConclusionsNon-intubated opioid-sparing strategies for video-assisted lung resections reduce airway injury and promote postoperative recovery. Clinical trial number and registry URLChiCTR1800018198https://www.chictr.org.cn/showproj.aspx?proj=30780

Stress pulmonary circulation parameters assessed by a cardiovascular magnetic resonance in patients after a heart transplant

Rest pulmonary circulation parameters such as pulmonary transit time (PTT), heart rate corrected PTT (PTTc) and pulmonary transit beats (PTB) can be evaluated using several methods, including the first-pass perfusion from cardiovascular magnetic resonance. As previously published, up to 58% of patients after HTx have diastolic dysfunction detectable only in stress conditions. By using adenosine stress perfusion images, stress analogues of the mentioned parameters can be assessed. By dividing stress to rest biomarkers, potential new ratio parameters (PTT ratio and PTTc ratio) can be obtained. The objectives were to (1) provide more evidence about stress pulmonary circulation biomarkers, (2) present stress to rest ratio parameters, and (3) assess these biomarkers in patients with presumed diastolic dysfunction after heart transplant (HTx) and in childhood cancer survivors (CCS) without any signs of diastolic dysfunction. In this retrospective study, 48 patients after HTx, divided into subgroups based on echocardiographic signs of diastolic dysfunction (41 without, 7 with) and 39 CCS were enrolled. PTT was defined as the difference between the onset time of the signal intensity increase in the left and the right ventricle. PTT in rest conditions were without significant differences when comparing the CCS and HTx subgroup without diastolic dysfunction (4.96 ± 0.93 s vs. 5.51 ± 1.14 s, p = 0.063) or with diastolic dysfunction (4.96 ± 0.93 s vs. 6.04 ± 1.13 s, p = 0.13). However, in stress conditions, both PTT and PTTc were significantly lower in the CCS group than in the HTx subgroups, (PTT: 3.76 ± 0.78 s vs. 4.82 ± 1.03 s, p < 0.001; 5.52 ± 1.56 s, p = 0.002). PTT ratio and PTTc ratio were below 1 in all groups. In conclusion, stress pulmonary circulation parameters obtained from CMR showed prolonged PTT and PTTc in HTx groups compared to CCS, which corresponds with the presumption of underlying diastolic dysfunction. The ratio parameters were less than 1.

Non-Invasive Assessment of Congestion by Cardiovascular and Pulmonary Ultrasound and Biomarkers in Heart Failure.

Worsening chronic heart failure (HF) is responsible for recurrent hospitalization and increased mortality risk after discharge, irrespective to the ejection fraction. Symptoms and signs of pulmonary and systemic congestion are the most common cause for hospitalization of acute decompensated HF, as a consequence of increased cardiac filling pressures. The elevated cardiac filling pressures, also called hemodynamic congestion, may precede the occurrence of clinical congestion by days or weeks. Since HF patients often have comorbidities, dyspnoea, the main symptom of HF, may be also caused by respiratory or other illnesses. Recent studies underline the importance of the diagnosis and treatment of hemodynamic congestion before HF symptoms worsen, reducing hospitalization and improving prognosis. In this paper we review the role of integrated evaluation of biomarkers and imaging technics, i.e., echocardiography and pulmonary ultrasound, for the diagnosis, prognosis and treatment of congestion in HF patients.

Proteomics discovery of pulmonary hypertension biomarkers: Insulin-like growth factor binding proteins are associated with disease severity.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by sustained elevations of pulmonary artery pressure. To date, we lack circulating, diagnostic, and prognostic markers that correlate to clinical and functional parameters. In this study, we performed mass spectrometry‐based proteomics analysis to identify circulating biomarkers of PAH. Plasma samples from patients with idiopathic pulmonary arterial hypertension (IPAH, N = 9) and matched normal controls (N = 9) were digested with trypsin and analyzed using data‐dependent acquisition on an Orbitrap mass spectrometer. A total of 826 (false discovery rate [FDR] 0.047) and 461 (FDR 0.087) proteins were identified across all plasma samples obtained from IPAH and control subjects, respectively. Of these, 153 proteins showed >2 folds change (p < 0.05) between groups. Circulating levels of carbonic anhydrase 2 (CA2), plasma kallikrein (KLKB1), and the insulin‐like growth factor binding proteins (IGFBP1‐7) were quantified by immunoassay in an independent verification cohort (N = 36 PAH and N = 35 controls). CA2 and KLKB1 were significantly different in PAH versus control but were not associated with any functional or hemodynamic measurements. Whereas, IGFBP1 and 2 were associated with higher pulmonary vascular resistance, IGFBP2, 4, and 7 with decreased 6‐min walk distance (6MWD), and IGFBP1, 2, 4, and 7 with worse survival. This plasma proteomic discovery analysis suggests the IGF axis may serve as important new biomarkers for PAH and play an important role in PAH pathogenesis.

Comparative pulmonary toxicities of lunar dusts and terrestrial dusts (TiO2 & SiO2) in rats and an assessment of the impact of particle-generated oxidants on the dusts’ toxicities

Humans will set foot on the Moon again soon. The lunar dust (LD) is potentially reactive and could pose an inhalation hazard to lunar explorers. We elucidated LD toxicity and investigated the toxicological impact of particle surface reactivity (SR) using three LDs, quartz, and TiO2. We first isolated the respirable-size-fraction of an Apollo-14 regolith and ground two coarser samples to produce fine LDs with increased SR. SR measurements of these five respirable-sized dusts, determined by their in-vitro ability to generate hydroxyl radicals (•OH), showed that ground LDs > unground LD ≥ TiO2 ≥ quartz. Rats were each intratracheally instilled with 0, 1, 2.5, or 7.5 mg of a test dust. Toxicity biomarkers and histopathology were assessed up to 13 weeks after the bolus instillation. All dusts caused dose-dependent-increases in pulmonary lesions and toxicity biomarkers. The three LDs, which possessed mineral compositions/properties similar to Arizona volcanic ash, were moderately toxic. Despite a 14-fold •OH difference among these three LDs, their toxicities were indistinguishable. Quartz produced the lowest •OH amount but showed the greatest toxicity. Our results showed no correlation between the toxicity of mineral dusts and their ability to generate free radicals. We also showed that the amounts of oxidants per neutrophil increased with doses, time and the cytotoxicity of the dusts in the lung, which supports our postulation that dust-elicited neutrophilia is the major persistent source of oxidative stress. These results and the discussion of the crucial roles of the short-lived, continuously replenished neutrophils in dust-induced pathogenesis are presented.

Pulmonary Functions and Inflammatory Biomarkers in Post-Pulmonary Tuberculosis Sequelae.

Background Post-tuberculosis (TB) sequelae is a commonly encountered clinical entity, especially in high TB burden countries. This may represent chronic anatomic sequelae of previously treated TB, with frequent symptomatic presentation. This pilot study was aimed to investigate the pulmonary functions and systemic inflammatory markers in patients with post-TB sequelae (PTBS) and to compare them with post-TB without sequelae (PTBWS) participants and healthy controls.Methods A total of 30 participants were enrolled, PTBS (n=10), PTBWS (n=10), and healthy controls (n=10). Pulmonary function tests included spirometry and measurement of airway impedance by impulse oscillometry. Serum levels of matrix metalloproteinase (MMP)-1, transforming growth factor-β, and interferon-γ were estimated.Results Slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC, and peak expiratory flow were significantly lower in PTBS as compared to controls. SVC and FEV1 were significantly less in PTBS as compared to PTBWS. Total airway impedance (Z5), total airway resistance (R5), central airway resistance (R20), area of reactance (Ax), and resonant frequency (Fres) were significantly higher and respiratory reactance at 5 and 20 Hz (X5, X20) were significantly lower in PTBS as compared to PTBWS. Spirometry parameters correlated with impulse oscillometry parameters in PTBS. Serum MMP-1 level was significantly higher in PTBS as compared to other groups.Conclusion Significant pulmonary function impairment was observed in PTBS, and raised serum MMP-1 levels compared with PTBWS and healthy controls. Follow-up pulmonary function testing is recommended after treatment of TB for early diagnosis and treatment of PTBS.

Biomarker evaluation for prognostic stratification of patients with COVID-19: the added value of quantitative chest CT.

Aim: Pulmonary disease burden and biomarkers are possible predictors of outcomes in patients with COVID-19 and provide complementary information. In this study, the prognostic value of adding quantitative chest computed tomography (CT) to a multiple biomarker approach was evaluated among 148 hospitalized patients with confirmed COVID-19. Materials & methods: Patients admitted between March and July 2020 who were submitted to chest CT and biomarker measurement (troponin I, D-dimer and C-reactive protein) were retrospectively analyzed. Biomarker and tomographic data were compared and associated with death and intensive care unit admission. Results: The number of elevated biomarkers was significantly associated with greater opacification percentages, lower lung volumes and higher death and intensive care unit admission rates. Total lung volume <3.0 l provided further stratification for mortality when combined with biomarker evaluation. Conclusion: Adding automated CT data to a multiple biomarker approach may provide a simple strategy for enhancing risk stratification of patients with COVID-19.

Sustained and continued improvements in pulmonary function, hepatosplenomegaly, dyslipidemia, and disease biomarkers in 5 adults with chronic acid sphingomyelinase deficiency after 6.5 years of olipudase alfa enzyme replacement therapy

Sustained and continued improvements in pulmonary function, hepatosplenomegaly, dyslipidemia, and disease biomarkers in 5 adults with chronic acid sphingomyelinase deficiency after 6.5 years of olipudase alfa enzyme replacement therapy

Review: Serum Biomarkers of Lung Fibrosis in Interstitial Pneumonia with Autoimmune Features—What Do We Already Know?

Interstitial pneumonia with autoimmune features (IPAF) belongs to a group of diseases called interstitial lung diseases (ILDs), which are disorders of a varied prognosis and course. Finding sufficiently specific and sensitive biomarkers would enable the progression to be predicted, the natural history to be monitored and patients to be stratified according to their treatment. To assess the significance of pulmonary fibrosis biomarkers studied thus far, we searched the PubMed, Medline and Cochrane Library databases for papers published between January 2015 and June 2021. We focused on circulating biomarkers. A primary review of the databases identified 38 articles of potential interest. Overall, seven articles fulfilled the inclusion criteria. This review aims to assess the diagnostic and prognostic value of molecules such as KL-6, SP-A, SP-D, circulating fibrocytes, CCL2, CXCL13, CXCL9, CXCL10 and CXCL11. All of these biomarkers have previously been studied in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). IPAF is a disorder of a heterogeneous nature. It explains the lack of coherent observations in terms of correlations with functional parameters. There is still no meta-analysis of pulmonary fibrosis biomarkers in IPAF. This is mainly due to the heterogeneity of the methodology and groups analysed in the research. More research in this area is needed.