Chronic Interstitial Pneumonia Research Articles

Protective Effects of Tunisian Orange Co-Product Extract and Oleuropein-Hesperidin Combination on Bleomycin-Induced Pulmonary Fibrosis in Rats.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia that leads to acute lung damage, deterioration of lung function, and increased mortality risk. In this study, we investigated the effects of the orange coproduct extract (OCE) and the combination of pure hesperidin and oleuropein (HO) on an experimental model of pulmonary fibrosis induced by bleomycin (BLM) in Wistar rats. Rats were divided into six groups: the control group (G1), the BLM group (G2), three groups (G3, G4, G5) receiving a single dose of BLM combined with OCE extract at 100, 200, and 300 mg/kg, and group 6 (G6) receiving a single dose of BLM combined with HO: both pure major phenolic compounds of OCE (hesperidin at 50 mg/kg) and olive leaves (oleuropein at 2.5 mg/kg). Oxidative stress in lung tissues was investigated using catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) assays and the measurement of malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels. Treatment with OCE and HO normalized the disturbance in oxidative markers' levels and showed a significant reduction in fibrosis score with no renal or hepatic toxic effects. In conclusion, OCE and HO exhibit antifibrotic effects on a rat model of pulmonary fibrosis.

Native lung surgery after single lung transplantation: clinical characteristics and outcomes.

Single lung transplantation (SLT) is a viable option for patients with end-stage pulmonary parenchymal and vascular diseases. However, various diseases can occur in native lungs after SLT. Between January 2000 and December 2021, 35 patients underwent cadaveric SLT and survived for more than 30days in our hospital. Among these 35 patients, 10 required surgery for diseases that developed in their native lungs. The clinical characteristics of these 10 patients and the outcomes of native lung surgery (NLS) were investigated. Among these ten patients, the indications for lung transplantation were chronic obstructive pulmonary disease and idiopathic interstitial pneumonia in three patients each, and lymphangioleiomyomatosis and collagen vascular disease-related interstitial pneumoniain two patients each. The causes of NLS included pneumothorax (n = 4), primary lung cancer (n = 2), native lung hyperinflation (n = 2), and pulmonary aspergilloma (n = 2). The surgical procedures were pneumonectomy (n = 7), lobectomy (n = 2), and alveolar-pleural fistula repair (n = 1). Only one postoperative complication, empyema, was treated with antibiotics. The 5-year overall survival rates after transplantation with and without NLS were 70.0% and 80.0%, respectively, and did not differ to a statistically extent (p = 0.56). NLS is an effective treatment option for diseases that develop in the native lungs after SLT.

Efficacy and safety of pirfenidone according to clinical trials

The results of clinical studies on the use of pirfenidone in idiopathic pulmonary fibrosis (IPF) are presented. The purpose of this study was to analyze the effectiveness and safety of pirfenidone in IPF according to clinical studies published in the scientific literature. IPF occupies an important place in the structure of interstitial lung diseases. Currently, IPF is understood as a condition in which there is chronic progressive fibrotic interstitial aseptic pneumonia of unknown etiology, quickly leading to disability and death. The antifibrotic drug pirfenidone has been approved by the EMA and FDA for use in patients with IPF. The clinical efficacy and safety of pirfenidone have been demonstrated in randomized clinical trials. When using pirfenidone, there were 47.9 % fewer patients with an absolute decrease in FVC ≥10 % or who died, and 132.5 % more patients with no decrease in FVC (p <0.001). In addition, the pirfenidone group had significantly better 6-minute walk test scores (p=0.04) and significantly improved progression-free survival (p<0.001). Long-term use of pirfenidone (up to 72 weeks) significantly reduced the rate of decline in FVC, prevented a reduction in distance traveled in the 6-minute walk test, and increased the time until signs of disease progression appeared compared with placebo. Pirfenidone demonstrated a good safety profile; in most cases, adverse effects were mild, disappeared when the drug dose was reduced, and had no adverse long-term consequences. As a result of a generalized analysis of adverse events recorded in the CAPACITY, ASCEND, and RECAP studies, it was found that long-term (maximum duration was 9.9 years) treatment with pirfenidone was accompanied by nausea in 37.6 % of cases, diarrhea in 28.1 %, dyspepsia — in 18.4 %, vomiting — in 15.9 %, and skin rashes — in 25.0 %.

Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction

BackgroundIdiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates. Recently, the quest for trustworthy biomarkers for IPF has gained momentum. Notably, emerging studies indicate that circular RNAs (circRNAs) found in exosomes may hold significant potential as valuable diagnostic markers.MethodsIn this study, we initially explored the expression profile of circRNAs in exosomes sourced from the blood of IPF patients and healthy volunteers, employing a human circRNA microarray. We then utilized RT-qPCR to corroborate the dysregulated circRNAs identified by the microarray during the training phase. Next, the circRNAs that displayed a significant increase during the training phase were selected for further validation in a larger cohort encompassing 113 IPF patients and 76 healthy volunteers. Ultimately, the expression level and function of hsa_circ_0044226 were substantiated through a series of in vivo and in vitro experiments.ResultsUtilizing a human circRNA microarray, we identified 11 dysregulated circRNAs in the exosomes derived from the blood of IPF patients and control volunteers. Subsequent RT-qPCR analysis revealed significant increases in three circRNAs (hsa_circ_0044226, hsa_circ_0004099, hsa_circ_0008898) within the IPF patients. Notably, hsa_circ_0044226 was markedly elevated in patients experiencing acute exacerbation of IPF (AE-IPF) compared to those with stable IPF (S-IPF). Additionally, an upregulation of hsa_circ_0044226 was observed in the blood exosomes derived from a bleomycin-induced IPF mouse model.ConclusionThe expression levels of hsa_circ_0044226, hsa_circ_0004099, and hsa_circ_0008898 in plasma exosomes introduce a new paradigm of biomarkers for the diagnosis and progression of IPF.

Immune checkpoint inhibitors in patients with lung cancer having chronic interstitial pneumonia.

In interstitial pneumonia (IP)-associated lung cancer, immune checkpoint inhibitor pneumonitis (ICIP) is common with immune checkpoint inhibitor (ICI) treatment. The purpose of the present study was to clarify the safety and efficacy of ICI treatment for patients with lung cancer with IP. This multicentre retrospective observational study was conducted from June 2016 to December 2020 in patients with primary lung cancer with IP who received ICI treatment. A total of 200 patients (median age 70 years; male/female, 176/24) were enrolled from 27 institutions. ICIP occurred in 61 patients (30.5%), pneumonitis grades 3-5 in 32 patients (15.5%) and death in nine patients (4.5%). The common computed tomography pattern of ICIP was organising pneumonia in 29 patients (47.5%). Subsequently, diffuse alveolar damage (DAD) pattern was observed in 19 patients (31.1%) who had a significantly worse prognosis than those with a non-DAD pattern (median progression-free survival (PFS) 115 days versus 226 days, p=0.042; median overall survival (OS) 334 days versus 1316 days, p<0.001). Immune-related adverse events (irAEs) occurred in approximately 50% of patients. Patients with irAEs (n=100) had a better prognosis than those without irAEs (n=100) (median PFS 200 days versus 77 days, p<0.001; median OS 597 days versus 390 days p=0.0074). The objective response rate and disease control rate were 41.3% and 68.5%, respectively. Although ICI treatment was effective for patients with lung cancer with IP, ICIP developed in approximately 30% of patients. Patients with irAEs had a significantly better PFS and OS than those without irAEs.

Long-Lasting SARS-CoV-2 Infection With Post-COVID-19 Chronic Interstitial Pneumonia in a Patient With Chronic Lymphocytic Leukemia Treated Successfully With Intravenous Immunoglobulin

Long-Lasting SARS-CoV-2 Infection With Post-COVID-19 Chronic Interstitial Pneumonia in a Patient With Chronic Lymphocytic Leukemia Treated Successfully With Intravenous Immunoglobulin

Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk. We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p<4.5×10-4 and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report. The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies. Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.

Features of the course of idiopathic fibrosing alveolitis

Idiopathic pulmonary fibrosis (IPF) is a special form of chronic progressive fibrosing interstitial pneumonia of unknown etiology; it occurs predominantly in elderly people, affects only the lungs, and is associated with the histological and/or radiological pattern of common interstitial pneumonia. The frequency of this pathology has been increasing in recent years. A timely diagnosis and treatment can slow down the progression of the disease and prevent the need for lung transplantation.

EP12.01-51 Clinical Significance of Chronic Interstitial Pneumonia Induced by EGFR-TKI Administration

EP12.01-51 Clinical Significance of Chronic Interstitial Pneumonia Induced by EGFR-TKI Administration

An outbreak of small ruminant lentivirus in a Swedish dairy goat herd

AbstractSmall ruminant lentivirus causes severe economic losses, and negatively affects animal welfare in goat herds across the world. The aim of this study was to describe the clinical and pathological consequences of the disease in an affected goat herd, as well as to sequence the virus in infected animals. Seventy‐six percent of the sampled animals were small ruminant lentivirus seropositive. The most prominent signs of disease were respiratory signs found in clinical examinations and chronic interstitial pneumonia found at postmortem examination. All animals with pneumonia also showed evidence of infection with Muellerius capillaris. The cell count in bulk milk was high and most likely related to the high small ruminant lentivirus seroprevalence within the herd. Small ruminant lentivirus was successfully detected in the lungs, bronchial lymph nodes and udder tissues using polymerase chain reaction. The phylogenetic analysis of the obtained sequences revealed the highest similarity with small ruminant lentiviruses in group C, which consists of viruses which have previously been found in Norwegian goats and sheep.

Engineering Ferroptosis Inhibitors as Inhalable Nanomedicines for the Highly Efficient Treatment of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) refers to chronic progressive fibrotic interstitial pneumonia. It is called a "tumor-like disease" and cannot be cured using existing clinical drugs. Therefore, new treatment options are urgently needed. Studies have proven that ferroptosis is closely related to the development of IPF, and ferroptosis inhibitors can slow down the occurrence of IPF by chelating iron or reducing lipid peroxidation. For example, the ferroptosis inhibitor deferoxamine (DFO) was used to treat a mouse model of pulmonary fibrosis, and DFO successfully reversed the IPF phenotype and increased the survival rate of mice from 50% to 90%. Given this, we perceive that the treatment of IPF by delivering ferroptosis inhibitors is a promising option. However, the delivery of ferroptosis inhibitors faces two bottlenecks: low solubility and targeting. For one thing, we consider preparing ferroptosis inhibitors into nanomedicines to improve solubility. For another thing, we propose to deliver nanomedicines through pulmonary drug-delivery system (PDDS) to improve targeting. Compared with oral or injection administration, PDDS can achieve better delivery and accumulation in the lung, while reducing the systemic exposure of the drug, and is an efficient and safe drug-delivery method. In this paper, three possible nanomedicines for PDDS and the preparation methods thereof are proposed to deliver ferroptosis inhibitors for the treatment of IPF. Proper administration devices and challenges in future applications are also discussed. In general, this perspective proposes a promising strategy for the treatment of IPF based on inhalable nanomedicines carrying ferroptosis inhibitors, which can inspire new ideas in the field of drug development and therapy of IPF.

Angiopoietin-like 4 Is a Critical Regulator of Fibroblasts during Pulmonary Fibrosis Development.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible interstitial pneumonia caused by the excessive production and deposition of extracellular matrix components, including type I collagen. Activated fibroblasts, called α-SMA (α-smooth muscle actin)-expressing myofibroblasts, are the major source of type I collagen in pulmonary fibrosis (PF), but the mechanisms underlying disease progression have not been fully elucidated. Here, we obtained lung fibroblasts from patients with IPF from both nonfibrotic and fibrotic areas as determined by a lung computed tomography scan and compared gene expression between these areas by DNA microarray. We found that ANGPTL4 (angiopoietin-like 4) was highly expressed only in fibroblasts from the fibrotic area. ANGPTL4 was selectively expressed in the fibroblastic area of IPF lungs, where the myofibroblast marker α-SMA was also expressed. ANGPTL4 also regulates the gene expression of fibrosis-related markers, cell migration, and proliferation. In addition, ANGPTL4 expression in a murine model of PF induced by treatment with bleomycin was significantly induced in the lungs from the acute to the chronic phase. Single-cell transcriptome analysis during the course of bleomycin-induced PF revealed that Angptl4 was predominantly expressed in the activated fibroblasts and myofibroblasts. Moreover, the administration of recombinant ANGPTL4 to the bleomycin-induced fibrosis model significantly increased collagen deposition and exacerbated the PF. In contrast, the pathogenesis of PF in Angptl4-deficient mice was improved. These results indicate that ANGPTL4 is critical for the progression of PF and might be an early diagnostic marker and therapeutic target for IPF.

Hypersensitivity pneumonitis: Principles in diagnosis and management.

Hypersensitivity pneumonitis: Principles in diagnosis and management.

Histopathological, biochemical and molecular studies on a model of systemic autoimmune disease induced by sodium silicate in non-genetically prone rats

Sodium silicate (Na2SiO3) is an inorganic silica salt used in many products. Few studies reported autoimmune diseases (AIDs) due to Na2SiO3 exposure. This study investigates the role of Na2SiO3 exposure by different routes and doses in AID development in rats. We assigned 40 female rats to four groups: G1 control group, G2 rats were subcutaneously injected with 5 mg Na2SiO3 suspension, and G3 and G4 rats were orally administered 5 mg and 7 mg Na2SiO3 suspension, respectively. Na2SiO3 was administered weekly for 20 weeks. Serum anti-nuclear antibodies (ANA) detection, histopathology of kidney, brain, lung, liver, and heart, oxidative stress biomarkers (MDA and GSH) in tissues, Matrix metalloproteinase activity in serum, TNF-α, and Bcl-2 expression in tissues were performed. ANA was significantly increased in silicate groups, especially G2. Creatinine was significantly increased in silicate groups. Histopathology revealed vasculitis and fibrinoid degeneration of blood vessels, a picture of immune-mediated glomerulonephritis in the kidneys, and chronic interstitial pneumonia with medial hypertrophy of pulmonary blood vessels. The activity of gelatinases (MMP-2 and MMP-9) and collagenase (MMP-13), which play role in inflammation, remodeling, and immune complex degradation, were significantly increased in the silicate-exposed groups. Bcl-2 was significantly decreased, indicating apoptosis. Therefore, oral administration and subcutaneous injection of Na2SiO3 induced immune-mediated glomerulonephritis with elevated ANA levels and overexpression of TNF-α in rats.

Short Telomere Syndrome presenting with pulmonary fibrosis, liver cirrhosis and hepatopulmonary syndrome: a case report

BackgroundIdiopathic pulmonary fibrosis is thought to result from aberrant post-injury activation of epithelial cells leading to fibroblast proliferation and activation. A number of genetic aetiologies have been implicated in this disease process, including, among others, the short telomere syndromes. Short telomere syndromes follow an autosomal dominant pattern of inheritance resulting in shortened telomere length, which consequently leads to accelerated cell death. Organs with rapid cell turnover are most affected.Case presentationWe describe a case of a 53-year-old man with a chief complaint of cough and dyspnea on exertion. His presentation was otherwise significant for features of accelerated aging, including a history of osteoporosis and early greying, and a family history of pulmonary fibrosis in his father. Pulmonary function testing revealed a restrictive pattern with severely reduced diffusion capacity and high resolution CT of the chest showed diffuse lung disease with mild fibrosis, in pattern suggesting an alternative diagnosis to IPF. Biopsy of the lung was in keeping with chronic fibrosing interstitial pneumonia. Imaging of the abdomen showed splenomegaly, hepatic cirrhosis and portal hypertension. Transthoracic contrast echocardiogram showed intrapulmonary shunting consistent with hepatopulmonary syndrome. Given the constellation of early aging, idiopathic pulmonary fibrosis, cryptogenic cirrhosis and a family history of pulmonary fibrosis in this patient, the Short Telomere Syndrome was suspected. Peripheral blood was sent for Flow-cytometry FISH, which demonstrated granulocyte telomere length below the 10th percentile for the patient’s age, consistent with a diagnosis of Short Telomere Syndrome in this clinical context. Targeted genetic testing of mutations known to be associated with short telomere was negative though it was acknowledged that the full spectrum of disease-causing mutations remains unknown. Given the extensive fibrosis on biopsy and his progressive hypoxemia he was treated with mycophenolate and prednisone. Ultimately, he developed progressive respiratory failure and underwent double lung and concurrent liver transplant 18 months after the initial diagnosis was made.ConclusionsShort Telomere Syndrome is a rare cause of end stage organ disease and testing lacks sensitivity making diagnosis challenging. Organ transplant is still the mainstay of treatment. Nevertheless, disease identification is important because of implications for family member screening and the possibility of future treatment options.

Clinical results of carbon ion radiotherapy for inoperable stage I non-small cell lung cancer: A Japanese national registry study (J-CROS-LUNG)

Background and purposeRadiotherapy is a standard treatment for inoperable stage I non-small cell lung cancer (NSCLC), and carbon-ion radiation therapy (CIRT) may be used for such treatment. Although CIRT for stage I NSCLC has demonstrated favorable outcomes in previous reports, the reports covered only single-institution studies. We conducted a prospective nationwide registry study including all CIRT institutions in Japan. Materials and methodsNinety-five patients with inoperable stage I NSCLC were treated by CIRT between May 2016 and June 2018. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. ResultsThe median patient age was 77 years. Comorbidity rates for chronic obstructive pulmonary disease and interstitial pneumonia were 43% and 26%, respectively. The most common schedule for CIRT was 60 Gy (relative biological effectiveness (RBE)) in four fractions, and the second most common was 50 Gy (RBE) in one fraction. The 3-year overall survival, cause-specific survival, and local control rates were 59.3%, 77.1%, and 87.3%, respectively. Female sex and ECOG performance status of 0–1 were favorable prognostic factors for overall survival in a multivariate analysis. No grade 4 or higher adverse event was observed. The 3-year cumulative incidence of grade 2 or higher radiation pneumonitis was 3.2%. The risk factors for grade 2 or higher radiation pneumonitis were a force expiratory volume in 1 second (FEV1) of <0.9 L and a total does of ≥ 67 Gy(RBE). ConclusionThis study provides real-world treatment outcomes of CIRT for inoperable.stage I NSCLC in Japan.

Validity of diagnoses of respiratory diseases recorded in a Japanese administrative database

BackgroundValidating the information recorded in administrative databases is essential. However, no study has comprehensively validated the accuracy of Japanese Diagnosis Procedure Combination (DPC) data on various respiratory diseases. Therefore, this study aimed to evaluate the validity of diagnoses of respiratory diseases in the DPC database. MethodsWe conducted chart reviews of 400 patients hospitalized in the departments of respiratory medicine in two acute-care hospitals in Tokyo, between April 1, 2019 and March 31, 2021, and used them as reference standards. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DPC data on 25 respiratory diseases were determined. ResultsSensitivity ranged from 22.2% (aspiration pneumonia) to 100% (chronic eosinophilic pneumonia and malignant pleural mesothelioma) and was <50% for eight diseases, while specificity was >90% for all diseases. PPV ranged from 40.0% (aspiration pneumonia) to 100% (coronavirus disease 2019, bronchiectasis, chronic eosinophilic pneumonia, pulmonary hypertension, squamous cell carcinoma, small cell carcinoma, lung cancer of other histological types, and malignant pleural mesothelioma) and was >80% for 16 diseases. Except for chronic obstructive pulmonary disease (82.9%) and interstitial pneumonia (other than idiopathic pulmonary fibrosis) (85.4%), NPV was >90% for all diseases. These validity indices were similar in both hospitals. ConclusionsThe validity of diagnoses of respiratory diseases in the DPC database was high in general, thereby providing an important basis for future studies.

Impaired Dynamic Response of Oxygen Saturation During the 6-min Walk Test Is Associated With Mortality in Chronic Fibrosing Interstitial Pneumonia.

The 6-min walk test (6MWT) is a common assessment of exercise-induced hypoxemia and exercise capacity used in patients with chronic fibrosing interstitial pneumonia (CFIP). However, whether the dynamic changes in SpO2 and heart rate during the 6MWT are associated with mortality in patients with CFIP has been undefined. This retrospective study enrolled 63 subjects with mild to severe CFIP who underwent the 6MWT. Subjects with CFIP were divided into 2 groups according to disease severity: mild, diffusing capacity of the lungs for carbon monoxide percentage predicted (%DLCO) > 55% and %FVC > 75%; and severe, %DLCO ≤ 55% and/or %FVC ≤ 75%. This study aimed to evaluate dynamic changes in the 6MWT including 6-min walk distance, change in SpO2 (ΔSpO2 ), SpO2 reduction time, SpO2 recovery time, change in heart rate (Δ heart rate), heart rate acceleration time, slope of heart rate acceleration, heart rate recovery at 1 min of rest after the 6MWT (HR-recovery), and dyspnea on exertion that are reflected by static pulmonary function and are related to exacerbation of CFIP and mortality. Compared with subjects with mild CFIP, subjects with severe CFIP had significantly larger ΔSpO2 and longer SpO 2 reduction time and recovery time. The slope of heart rate, heart rate immediately after the 6MWT, and HR-recovery were lower in subjects with severe CFIP than in those with mild CFIP. In multiple regression analysis, percent vital capacity was significantly associated with SpO2 reduction time, and %DLCO was significantly associated with ΔSpO2 and SpO2 recovery time. Subjects with ΔSpO2 of > 10% and SpO2 recovery time of > 79 s had a significantly higher risk for exacerbation and mortality. Dynamic changes in SpO2 and heart rate during the 6MWT were associated with risk for exacerbation and mortality in subjects with CFIP. Impaired dynamic response of SpO2 could reflect likelihood of exacerbation and increased mortality in CFIP.

Combination of computed tomography imaging pattern and severity of respiratory failure as factors associated with prognosis for acute exacerbation of idiopathic chronic fibrosing interstitial pneumonia.

The prognosis of idiopathic chronic fibrotic interstitial pneumonitis (CFIP) in patients with acute exacerbation (AE) is variable. We examined whether the imaging pattern on thoracic computed tomography (CT) or the severity of respiratory failure with AE-CFIP is associated with short-term prognosis. Patients admitted to two university hospitals were retrospectively analyzed and divided into derivation and validation cohorts. The distribution of newly appearing parenchymal abnormalities on thoracic CT was classified into peripheral, multifocal, and diffuse patterns. Respiratory failure was defined as severe if a fraction of inspired oxygen ≥ 0.5 was required to maintain percutaneous oxygen saturation ≥ 90% on admission. Factors associated with 90 day-mortality were analyzed using univariate and Cox proportional hazard regression. In 59 patients with AE-CFIP of the derivation cohort, diffuse pattern on CT was associated with higher mortality within 90 days (43%) than peripheral/multifocal pattern (17%, p = 0.03). Additionally, compared with non-severe failure, severe respiratory failure was associated with higher mortality (47% vs. 21%, p = 0.06). Cox proportional hazard regression analysis demonstrated that a combination of diffuse pattern on CT and severe respiratory failure was associated with the poorest prognosis (hazard ratio [HR] 3.51 [interquartile range 1.26-9.80], p = 0.016) in the derivation cohort, which was confirmed in the validation cohort (n = 31, HR 4.30 [interquartile range 1.51-12.2], p = 0.006). The combination of imaging pattern on thoracic CT and severity of respiratory failure was associated with the prognosis of idiopathic AE-CFIP.

BAL Proteomic Signature of Lung Adenocarcinoma in IPF Patients and Its Transposition in Serum Samples for Less Invasive Diagnostic Procedures.

Idiopathic pulmonary fibrosis (IPF) is a form of chronic and irreversible fibrosing interstitial pneumonia of unknown etiology. Although antifibrotic treatments have shown a reduction of lung function decline and a slow disease progression, IPF is characterize by a very high mortality. Emerging evidence suggests that IPF increases the risk of lung carcinogenesis. Both diseases show similarities in terms of risk factors, such as history of smoking, concomitant emphysema, and viral infections, besides sharing similar pathogenic pathways. Lung cancer (LC) diagnosis is often difficult in IPF patients because of the diffuse lung injuries and abnormalities due to the underlying fibrosis. This is reflected in the lack of optimal therapeutic strategies for patients with both diseases. For this purpose, we performed a proteomic study on bronchoalveolar lavage fluid (BALF) samples from IPF, LC associated with IPF (LC-IPF) patients, and healthy controls (CTRL). Molecular pathways involved in inflammation, immune response, lipid metabolism, and cell adhesion were found for the dysregulated proteins in LC-IPF, such as TTHY, APOA1, S10A9, RET4, GDIR1, and PROF1. The correlation test revealed a relationship between inflammation- and lipid metabolism-related proteins. PROF1 and S10A9, related to inflammation, were up-regulated in LC-IPF BAL and serum, while APOA1 and APOE linked to lipid metabolism, were highly abundant in IPF BAL and low abundant in IPF serum. Given the properties of cytokine/adipokine of the nicotinamide phosphoribosyltransferase, we also evaluated its serum abundance, highlighting its down-regulation in LC-IPF. Our retrospective analyses of BAL samples extrapolated some potential biomarkers of LC-IPF useful to improve the management of these contemporary pathologies. Their differential abundance in serum samples permits the measurement of these potential biomarkers with a less invasive procedure.