Prognosis Of Idiopathic Pulmonary Fibrosis Research Articles

Prognosis of pulmonary fibrosis presenting with a usual interstitial pneumonia pattern on computed tomography in patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis: a retrospective single-center study

BackgroundMyeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis (MPO-ANCA nephritis) is occasionally accompanied by lung abnormalities such as pulmonary fibrosis. However, the clinical features of pulmonary fibrosis in patients with MPO-ANCA nephritis have not been well documented. This study was performed to compare the prognosis of a usual interstitial pneumonia (UIP) pattern of lung fibrosis in patients with MPO-ANCA nephritis with the prognosis of idiopathic pulmonary fibrosis (IPF).MethodsWe retrospectively reviewed the medical records of 126 patients with MPO-ANCA nephritis and identified 31 with a UIP pattern of lung fibrosis on high-resolution or thin-slice computed tomography (CT). We compared the characteristics and prognosis of these patients with those of 32 patients with IPF. In 18 patients from both groups, we assessed and compared the decline in lung volume over time using three-dimensional (3D) CT images reconstructed from thin-section CT data.ResultsThe numbers of male and female patients were nearly equal among patients with MPO-ANCA nephritis exhibiting a UIP pattern; in contrast, significant male dominancy was observed among patients with IPF (p = 0.0021). Significantly fewer smokers were present among the patients with MPO-ANCA nephritis with a UIP pattern than among those with IPF (p = 0.0062). There was no significant difference in the median survival time between patients with MPO-ANCA nephritis with a UIP pattern (50.8 months) and IPF (55.8 months; p = 0.65). All patients with IPF in this cohort received antifibrotic therapy (pirfenidone or nintedanib). Almost half of the deaths that occurred in patients with MPO-ANCA nephritis with a UIP pattern were caused by non-respiratory-related events, whereas most deaths in patients with IPF were caused by respiratory failure such as acute exacerbation. In the 3D CT lung volume analyses, the rate of decline in lung volume was equivalent in both groups.ConclusionsMPO-ANCA nephritis with a UIP pattern on CT may have an unfavorable prognosis equivalent to that of IPF with a UIP pattern treated with antifibrotic agents.

WBC COUNT AS A PROGNOSTIC INDICATOR IN THE TREATMENT OF IDIOPATHIC PULMONARY FIBROSIS

SESSION TITLE: Tuesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive form of interstitial lung disease resulting in varying degrees of scarring that is further exacerbated by acute inflammatory processes. White blood cell (WBC) count has been established as an inflammatory marker and is a known prognostic indicator in several cardiopulmonary processes. For IPF patients on disease-modifying therapy such as nintedanib or pirfenidone, the correlation between WBC and disease-related events has not been well studied. METHODS: Patient demographics, complete blood cell (CBC) counts, and pulmonary function tests from patients with IPF evaluated at Inova Fairfax Hospital between October 2014 and January 2019 were collected. CBCs were compared before and after initiation of anti-fibrotic therapy. Outcome events collated were respiratory hospitalizations, lung transplant, or death following the initiation of anti-fibrotic therapy. Event-free survival was calculated and compared between patients on nintedanib versus pirfenidone. RESULTS: Sixty-one patients with IPF had CBCs available prior to initiation of anti-fibrotic therapy. WBC range was 3.5 to 16.0 (median 8.0). Subsequently, 28 patients had been started on pirfenidone and 33 patients had been prescribed nintedanib. Of the 61 patients, those with baseline WBC count less than 8 (N=32) had a median event-free survival of 710 days (P=NS) compared with 703 days (P=NS) for those with baseline WBC count greater than 8 (N=29). The median change in WBC count amongst the 61 patients was -0.3. Median event-free survival for those with an increase in WBC count (N=23) after initiating anti-fibrotic therapy was 683 days (P=NS) compared with 761 days (P=NS) for those with no change or a decrease in WBC count (N=38). CONCLUSIONS: Trending the change in WBC count in patients with IPF on anti-fibrotic therapy did not serve as a prognostic indicator with statistical significance. This result may have been influenced by the small sample size of the study. Additionally, although WBC count has been suggested as a biomarker of prognosis in IPF, the mechanism of action of anti-fibrotic therapy may be independent of factors that influence the WBC count. CLINICAL IMPLICATIONS: Based on the findings of this study, further research is indicated to investigate the potential significance of WBC count and its role in inflammation in the evolution of IPF and its management. DISCLOSURES: No relevant relationships by Scott Barnett, source=Web Response Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 Added 03/15/2019 by Anne Brown, source=Web Response, value=Honoraria Consultant relationship with Promedior Please note: $5001 - $20000 Added 03/15/2019 by Anne Brown, source=Web Response, value=Consulting fee No relevant relationships by Talha Demirci, source=Web Response Speaker/Speaker's Bureau relationship with Genentech Please note: $1001 - $5000 Added 03/08/2019 by Christopher King, source=Web Response, value=Honoraria Consultant relationship with Roche-Genentech Please note: $20001 - $100000 Added 03/15/2019 by Steven Nathan, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Boerhinger-Ingelheim Please note: $20001 - $100000 Added 03/15/2019 by Steven Nathan, source=Web Response, value=Honoraria Consultant relationship with Promedior Please note: $5001 - $20000 Added 03/15/2019 by Steven Nathan, source=Web Response, value=Consulting fee Consultant relationship with Bellerophon Please note: $5001 - $20000 Added 03/15/2019 by Steven Nathan, source=Web Response, value=Consulting fee Advisory Committee Member relationship with United Therapeutics Please note: $1001 - $5000 Added 03/15/2019 by Steven Nathan, source=Web Response, value=Consulting fee

A HEATED SITUATION: THERMAL INJURY INDUCING AN IDIOPATHIC PULMONARY FIBROSIS EXACERBATION

A HEATED SITUATION: THERMAL INJURY INDUCING AN IDIOPATHIC PULMONARY FIBROSIS EXACERBATION

AUTOMATED MEASURED CT LUNG VOLUME CORRELATED WITH FVC IN IDIOPATHIC PULMONARY FIBROSIS

SESSION TITLE: Wednesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: The purpose of this study is to evaluate the relationship between automated measured CT lung volume and pulmonary function test parameters in patients with idiopathic pulmonary fibrosis (IPF). METHODS: Automated 3D volume reconstruction and measurement were performed with commercially available software (Syngo.Via, Siemens Healthineers, Forchheim, Germany) for CT of 78 IPF patients(M:F=58:20; mean age, 66.9 years; median follow up, 39 months). Correlation analysis was performed to assess the relationship between CT lung volume measurement and PFT parameters. The PFT parameters were used within three months of the CT scan. RESULTS: In the initial evaluation, the mean CT lung volume (3.33 ± 0.98L) was larger than the mean FVC (2.59 ± 0.78L) and lower than the mean TLC (4.01 ± 1.01L). And the automated measured CT lung volume correlated well with FVC (r= 0.78; p < 0.001) and TLC (r=0.77; p < 0.001). Annual decline of FVC was 256 ± 477 ml annual decline of CT lung volume was 221 ± 602 ml. And there were significant correlations between annual change of CT lung volume and annual change of FVC(r=0.55; p <0.001). CONCLUSIONS: Automated measured CT lung volume correlated well with FVC and TLC. And there were significant correlations between changes of CT lung volume and FVC. CLINICAL IMPLICATIONS: The change of FVC is very commonly used surrogate marker of prognosis of IPF. However, performing PFT is sometimes difficult for patient with IPF especially in advanced disease. If lung volume extracted from CT correlated well with FVC, IPF patients need not to perform PFT. DISCLOSURES: No relevant relationships by Soohyun Bae, source=Web Response No relevant relationships by Yangjin Jegal, source=Web Response No relevant relationships by WOORI JO, source=Web Response no disclosure on file for Byung Ju Kang; No relevant relationships by Jin Hyoung Kim, source=Web Response no disclosure on file for Soyeoun Lim; No relevant relationships by Kwang Won Seo, source=Web Response

Independent Clinical Factors Relevant to Prognosis of Patients with Idiopathic Pulmonary Fibrosis

BackgroundThe prognosis of idiopathic pulmonary fibrosis (IPF) is the worst among all interstitial lung diseases, and is related to the disease itself. Comorbidities or complications can worsen IPF. We assessed the effect of comorbidities on the survival of IPF patients. A retrospective review of patients with IPF was completed.Material/MethodsInformation on demographic features, clinical examination, and comorbidities at baseline were obtained. Then, median, 1-year, and 5-year survival was calculated. A total of 380 patients with IPF admitted to Beijing Chao-Yang Hospital from 1 April 2002 to 31 March 2015 were followed up until December 2016.ResultsOf these 380 patients, 71.9% died during the study period. Median survival was 2.25 years and overall 5-year survival was 28.5%. Also, 86.3% of patients were males. A total of 248 cases underwent lung function tests, and 178 patients underwent bronchoalveolar lavage (BAL). Multivariate analyses showed that forced expiratory volume in 1 second/forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide percent predicted, FVC% predicted, the number of macrophages, neutrophils, and lymphocytes in BAL fluid, pulmonary hypertension, hypoxemia, and hydropower disorder were independent prognostic indicators of IPF, GAP gender (G), age (A), and 2 pulmonary physiological parameters (P) model can help to predict prognosis of IPF.ConclusionsSpirometry, GAP model, and BAL are helpful to forecast the prognosis of IPF. IPF patients also suffering from pulmonary arterial hypertension, hypoxemia, and hydropower disorder have a poor prognosis.

The Tyrosine Kinase Inhibitor TAS-115 Attenuates Bleomycin-induced Lung Fibrosis in Mice.

The signaling pathways of growth factors, including platelet-derived growth factor, can be considered specific targets for overcoming the poor prognosis of idiopathic pulmonary fibrosis. Nintedanib, the recently approved multiple kinase inhibitor, has shown promising antifibrotic effects in patients with idiopathic pulmonary fibrosis; however, its efficacy is still limited, and in some cases, treatment discontinuation is necessary owing to toxicities such as gastrointestinal disorders. Therefore, more effective agents with less toxicity are still needed. TAS-115 is a novel multiple tyrosine kinase inhibitor that preferably targets platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor, and c-FMS in addition to other molecules. In this study, we evaluated the antifibrotic effect of TAS-115 on pulmonary fibrosis in vitro and in vivo. TAS-115 inhibited the phosphorylation of PDGFR on human lung fibroblast cell line MRC-5 cells and suppressed their platelet-derived growth factor-induced proliferation and migration. Furthermore, TAS-115 inhibited the phosphorylation of c-FMS, a receptor of macrophage colony-stimulating factor, in murine bone marrow-derived macrophages and decreased the production of CCL2, another key molecule for inducing pulmonary fibrosis, under the stimulation of macrophage colony-stimulating factor. Importantly, the inhibitory effects of TAS-115 on both PDGFR and c-FMS were 3- to 10-fold higher than those of nintedanib. In a mouse model of bleomycin-induced pulmonary fibrosis, TAS-115 significantly inhibited the development of pulmonary fibrosis and the collagen deposition in bleomycin-treated lungs. These data suggest that strong inhibition of PDGFR and c-FMS by TAS-115 may be a promising strategy for overcoming the intractable pathogenesis of pulmonary fibrosis.

Can monocytes predict prognosis of idiopathic pulmonary fibrosis?

Can monocytes predict prognosis of idiopathic pulmonary fibrosis?

Thoracic skeletal muscle quantification: low muscle mass is related with worse prognosis in idiopathic pulmonary fibrosis patients

BackgroundSarcopenia can contribute to negative outcomes in patients with various lung diseases. However, whether sarcopenia affects prognosis in patients with idiopathic pulmonary fibrosis (IPF) has not been reported. Simple measures of muscle mass, derived from chest computed tomography (CT), are increasingly being used to identify patients with sarcopenia. We hypothesized that skeletal muscle mass could be a predictor of prognosis in IPF patients.MethodsWe retrospectively evaluated 180 patients diagnosed with IPF between January 2010 and December 2015 at a tertiary care hospital in South Korea. We measured thoracic muscle volume by using the cross-sectional area (CSA) of the pectoralis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA) and the erector spinae muscle (ESMCSA) at the 12th vertebral region. CT scans at the time of diagnosis were used for analysis and respective CSA were divided by height squared to normalize for stature. Survival times were estimated with the Kaplan–Meier method and compared with the log-rank test. Multivariate Cox proportional hazards models were performed to investigate relationships between clinical parameters and mortality.ResultsMale patients in the lowest quartile of T4CSA divided by height squared (m2) (T4MI) and in the lowest quartile of ESMCSA divided by height squared (m2) (T12MI) were more likely to have higher Gender-Age-Physiology Index scores (T4MI, 3.3 ± 1.3 vs 4.0 ± 1.6, P = 0.012; T12MI, 3.2 ± 1.3 vs 4.1 ± 1.6, P = 0.002). Male patients in the lowest quartile of T4MI exhibited a significantly lower survival rate (P = 0.035). After multivariate Cox proportional hazards analysis, T4MI was a significant risk factor for all-cause mortality (HR, 0.955; 95% CI, 0.913–0.998; P = 0.041), whereas T12MI was not (HR, 0.980; 95% CI, 0.856–1.121; P = 0.766).ConclusionsLow skeletal mass normalized for stature at the level of 4th vertebrae which can be acquired by quantifying thoracic skeletal muscle on single-slice axial chest CT, may be a strong risk factor for all-cause mortality in patients with IPF.Trial registrationThe research protocol was approved by the Institutional Review Board of Severance Hospital, South Korea (IRB No.4–2018-0454).

Secretory immunoglobulin A induces human lung fibroblasts to produce inflammatory cytokines and undergo activation.

Immunoglobulin (Ig)A is the most abundant immunoglobulin in humans, and in the airway mucosa secretory IgA (sIgA) plays a pivotal role in first-line defense against invading pathogens and antigens. IgA has been reported to also have pathogenic effects, including possible worsening of the prognosis of idiopathic pulmonary fibrosis (IPF). However, the precise effects of IgA on lung fibroblasts remain unclear, and we aimed to elucidate how IgA activates human lung fibroblasts. We found that sIgA, but not monomeric IgA (mIgA), induced interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production by normal human lung fibroblasts (NHLFs) at both the protein and mRNA levels. sIgA also promoted proliferation of NHLFs and collagen gel contraction comparable to with transforming growth factor (TGF)-β, which is involved in fibrogenesis in IPF. Also, Western blot analysis and real-time quantitative polymerase chain reaction (PCR) revealed that sIgA enhanced production of α-smooth muscle actin (α-SMA) and collagen type I (Col I) by NHLFs. Flow cytometry showed that NHLFs bound sIgA, and among the known IgA receptors, NHLFs significantly expressed CD71 (transferrin receptor). Transfection of siRNA targeting CD71 partially but significantly suppressed cytokine production by NHLFs co-cultured with sIgA. Our findings suggest that sIgA may promote human lung inflammation and fibrosis by enhancing production of inflammatory or fibrogenic cytokines as well as extracellular matrix, inducing fibroblast differentiation into myofibroblasts and promoting human lung fibroblast proliferation. sIgA's enhancement of cytokine production may be due partially to its binding to CD71 or the secretory component.

Characterization of CD28null T cells in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease, with unknown etiopathogenesis and suboptimal therapeutic options. Previous reports have shown that increased T cell numbers and CD28null phenotype is predictive of prognosis in IPF, suggesting that these cells might have a role in this disease. Flow cytometric analysis of explanted lung cellular suspensions showed a significant increase in CD8+ CD28null T cells in IPF relative to normal lung explants. Transcriptomic analysis of CD3+ T cells isolated from IPF lungs explants revealed a loss of CD28 transcript expression and elevation of proinflammatory cytokine expression in IPF relative to normal T cells. IPF lung explant derived T cells (enriched with CD28null T cells), but not normal donor lung CD28+ T cells induced dexamethasone resistant lung remodeling in humanized NSG mice. Finally, CD28null T cells expressed similar CTLA4 and significantly higher levels of PD-1 proteins relative to CD28+ T cells and blockade of either proteins in humanized NSG mice, using anti-CTLA4, or anti-PD1, mAb treatment accelerated lung fibrosis. Together, these results demonstrate that IPF CD28null T cells may promote lung fibrosis but the immune checkpoint proteins, CTLA-4 and PD-1, appears to limit this effect.

Identifying Barriers to Idiopathic Pulmonary Fibrosis Treatment: A Survey of Patient and Physician Views

Background: Antifibrotics are recommended for the treatment of individuals with idiopathic pulmonary fibrosis (IPF), but treatment use remains at ∼60%. Objective: To investigate the views of individuals with IPF and pulmonologists on the diagnosis and management of IPF to understand treatment patterns. Methods: Interviews and/or online surveys were completed by patients and pulmonologists from Canada, France, Germany, Italy, Spain, and the UK. Responses from physicians were analyzed by time between diagnosis and treatment initiation in the majority of patients with IPF (group A, > 4 months; group B, ≤4 months). Statistical comparisons between physicians were undertaken using z tests, with p < 0.05 considered statistically significant. Results: The physicians in group A saw fewer patients, were less comfortable discussing the IPF prognosis with patients, and had less belief in the benefits of antifibrotic treatments than the physicians in group B. These physicians’ attitudes contrasted with those of the patients, who wanted more information about the IPF prognosis and pharmacological treatment options at diagnosis and were more concerned about preventing disease progression than avoiding medication side effects. Differences between countries were found regarding physicians’ comfort in discussing the prognosis at diagnosis and access to care. Conclusions: Several barriers to antifibrotic treatment, principally reflecting the differing views and values of patients and physicians, were identified in this study, suggesting a need for better patient-physician communication about pharmacological therapy for IPF.

Impact of mediastinal lymph node enlargement on the prognosis of idiopathic pulmonary fibrosis.

BackgroundMediastinal lymph node enlargement (LNE) is common in idiopathic pulmonary fibrosis (IPF) and is known to be associated with the severity of lung fibrosis. However, the relationship between mediastinal LNE and the prognosis of IPF has not been determined to date.MethodsThis study included patients with IPF from the interstitial lung disease registry at Seoul National University Bundang Hospital, from January 2012 to March 2016. Two thoracic radiologists independently reviewed mediastinal LNE and lung parenchymal fibrosis and ground glass opacities in chest computed tomography scans of each patient, which were obtained upon diagnosis. Mortality and admission rates were analyzed.ResultsIn total, 132 patients (104 [78.8%] male; median age, 72 years; range, 51–84 years) were enrolled and 73 (55.3%) patients had mediastinal LNE (short axis ≥ 10 mm in diameter). Mortality was significantly higher among patients with LNE than among those without LNE (hazard ratio 2.26 [95% confidence interval 1.20–4.23], p = 0.011). Of the patients with LNE, 24.7% experienced acute exacerbation and 43.8% experienced hospital admission for respiratory causes, in comparison with 16.9% and 40.0% of patients without LNE respectively. Although patients with LNE had a tendency to have increased rate of acute exacerbation, it was not statistically significant.ConclusionMediastinal LNE in IPF is associated with increased mortality and its occurrence may be considered a poor prognostic factor in patients with IPF.

Visual HRCT Score to Determine Severity and Prognosis of Idiopathic Pulmonary Fibrosis

Visual HRCT Score to Determine Severity and Prognosis of Idiopathic Pulmonary Fibrosis

Association of serum tumor markers with interstitial lung disease in patients with or without connective tissue disease: A cross-sectional study

Background: Serum markers, such as Krebs von den Lungen-6 (KL-6), are reported to reflect the severity, progression and prognosis of idiopathic pulmonary fibrosis (IPF). We aimed to evaluate whether tumor markers could improve the diagnosis of connective tissue diseases (CTDs) and predict CTD-related interstitial lung diseases (ILDs) (CTD–ILD); and whether there was a significant difference between ILD patients with CTD and without CTD (non-CTD–ILD). Methods: In this study, 146 patients with ILD only, 61 with CTD–ILD, 102 with lung cancer (LC), 111 with COPD, and 46 with CTD were enrolled. Serum levels of several tumor markers were collected. Results: Compared with COPD, the serum levels of CEA, NSE, CYFRA21-1, CA19-9 and CA125 were higher, but the level of SCC was lower; meanwhile, there were significant differences in NSE, SCC, CYFRA21-1 and CA125 between CTD–ILD and non-CTD–ILD groups. Conclusions: It appears that tumor-associated antigens may be the predictive factors for CTD–ILD that could be used to identify CTD from ILD before it is detected on autoimmune symptoms or auto-antibodies. However, further studies are needed to validate our findings and determine whether serum tumor markers have prognostic value or predict progressive CTD–ILD.

Idiopathic pulmonary fibrosis: a clinical update.

Idiopathic pulmonary fibrosis (IPF) is the commonest interstitial lung disease (ILD) and is characterised by progressive scarring of the lungs. It typically presents in the sixth or seventh decade.1 The prognosis of IPF is poor and is worse than most cancers, with a median survival from diagnosis of 2.5–3.5 years.1 In 2012, over 5000 people died of IPF in the UK accounting for 1% of all deaths and 4.6% of respiratory deaths.2 On average, a general practice of 10 000 patients will see 2–3 new cases every 3 years,3 although this is likely to be an underestimate, contrasting with 500 per 10 000 for chronic obstructive pulmonary disease (COPD). The rising incidence and prevalence means that GPs will be pivotal in the early detection and long-term management of patients with IPF. Patients with IPF typically present first to their GP. Distinguishing these symptoms from more common conditions such as COPD can be challenging. A history of persistent progressive breathlessness and/or cough in a patient >45 years who may, but not exclusively, have velcro crackles on auscultation and finger clubbing should warrant further management with radiological imaging (chest X-ray and high-resolution computed tomography [Figure 1]) and/or referral to an IPF specialist. …

The Selective Angiotensin II Type 2 Receptor Agonist, Compound 21, Attenuates the Progression of Lung Fibrosis and Pulmonary Hypertension in an Experimental Model of Bleomycin-Induced Lung Injury.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease characterized by scar formation and respiratory insufficiency, which progressively leads to death. Pulmonary hypertension (PH) is a common complication of IPF that negatively impacts clinical outcomes, and has been classified as Group III PH. Despite scientific advances, the dismal prognosis of IPF and associated PH remains unchanged, necessitating the search for novel therapeutic strategies. Accumulating evidence suggests that stimulation of the angiotensin II type 2 (AT2) receptor confers protection against a host of diseases. In this study, we investigated the therapeutic potential of Compound 21 (C21), a selective AT2 receptor agonist in the bleomycin model of lung injury. A single intra-tracheal administration of bleomycin (2.5 mg/kg) to 8-week old male Sprague Dawley rats resulted in lung fibrosis and PH. Two experimental protocols were followed: C21 was administered (0.03 mg/kg/day, ip) either immediately (prevention protocol, BCP) or after 3 days (treatment protocol, BCT) of bleomycin-instillation. Echocardiography, hemodynamic, and Fulton's index assessments were performed after 2 weeks of bleomycin-instillation. Lung tissue was processed for gene expression, hydroxyproline content (a marker of collagen deposition), and histological analysis. C21 treatment prevented as well as attenuated the progression of lung fibrosis, and accompanying PH. The beneficial effects of C21 were associated with decreased infiltration of macrophages in the lungs, reduced lung inflammation and diminished pulmonary collagen accumulation. Further, C21 treatment also improved pulmonary pressure, reduced muscularization of the pulmonary vessels and normalized cardiac function in both the experimental protocols. However, there were no major differences in any of the outcomes measured from the two experimental protocols. Collectively, our findings indicate that stimulation of the AT2 receptor by C21 attenuates bleomycin-induced lung injury and associated cardiopulmonary pathology, which needs to be further explored as a promising approach for the clinical treatment of IPF and Group III PH.

EMPIRE Registry, Czech Part: Impact of demographics, pulmonary function and HRCT on survival and clinical course in idiopathic pulmonary fibrosis.

Prognostic factors of idiopathic pulmonary fibrosis (IPF) currently recognized include changes in vital capacity and radiologic findings. However, most of the prognostic studies in IPF are based on clinical studies with preselected IPF populations. Therefore, we decided to analyze the factors influencing IPF prognosis based on the real-practice data from our IPF registry. Data of 514 subjects consecutively entered since 2012 into Czech EMPIRE IPF registry were analyzed. Median age of our patient cohort was 67 years (50-82). Median overall survival (OS) of the cohort was 63.1 months. The clinical course of IPF according to FVC (forced vital capacity) changes was stabilized in 32.8% of patients (29.7% according to DLCO [diffuse lung capacity] changes), slowly progressive in 39.5% (45%), rapidly progressive in 23.5% (20.7%); and 1.7% patients had at least one acute exacerbation during follow-up. Deterioration in FVC of ≥10% at month 12 and in DLCO of ≥15% at months 12, 18, and 24 influenced the OS significantly. The fast progressors defined by the DLCO decline rate had higher risk of death compared to those defined by the FVC change over time. In multivariate analysis, age ≥70 years, interstitial HRCT scores ≥3, and change in DLCO of ≥15% at month 12 were confirmed as factors negatively influencing OS. DLCO changes over time were shown as a better predictor of mortality compared with FVC changes in our study. In our opinion it is necessary to implement the DLCO analysis into clinical trials and routine practice.

Genetics in Idiopathic Pulmonary Fibrosis Pathogenesis, Prognosis, and Treatment.

Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia (IIP), is characterized by irreversible scarring of the lung parenchyma and progressive decline in lung function leading to eventual respiratory failure. The prognosis of IPF is poor with a median survival of 3–5 years after diagnosis and no curative medical therapies. Although the pathogenesis of IPF is not well understood, there is a growing body of evidence that genetic factors contribute to disease risk. Recent studies have identified common and rare genetic variants associated with both sporadic and familial forms of pulmonary fibrosis, with at least one-third of the risk for developing fibrotic IIP explained by common genetic variants. The IPF-associated genetic loci discovered to date are implicated in diverse biological processes, including alveolar stability, host defense, cell–cell barrier function, and cell senescence. In addition, some common variants have also been associated with distinct clinical phenotypes. Better understanding of how genetic variation plays a role in disease risk and phenotype could identify potential therapeutic targets and inform clinical decision-making. In addition, clinical studies should be designed controlling for the genetic backgrounds of subjects, since clinical outcomes and therapeutic responses may differ by genotype. Further understanding of these differences will allow the development of personalized approaches to the IPF management.

Clinical impact of depression and anxiety in patients with idiopathic pulmonary fibrosis.

BackgroundAlthough depression and anxiety represent significant yet treatable comorbidities in patients with idiopathic pulmonary fibrosis (IPF), their impact on the clinical course and prognosis of IPF remain unclear.PurposeWe investigated the prevalence and clinical significance of depression and anxiety in patients with IPF.MethodsThe present study included a prospective cohort comprising 112 Korean patients with IPF who had completed the Hospital Anxiety and Depression Scale (HADS) questionnaire.ResultsSymptoms of depression and anxiety were present in 25.9% and 21.4% of patients with IPF, respectively (HADS scores ≥8). No significant differences in demographic data, age, sex, smoking status, Modified Medical Research Council Dyspnea Scale (MMRC) scores, pulmonary function tests, or Gender-Age-Physiology Index for IPF were observed between patients with depression or anxiety and those without. However, in patients with anxiety, St. George's Respiratory Questionnaire (SGRQ) scores were significantly higher than those of patients without anxiety (40.5 versus 23.5; p = 0.003). The survival rate and total number of hospital admissions did not significantly differ between patients with depression/anxiety and those without.ConclusionsOur findings indicate that depression and anxiety are relatively common in patients with IPF. Although no significant differences were noted with regard to survival rate and hospitalization, the present study suggests that depression and anxiety significantly influence quality of life in patients with IPF.

Impact of serum SP-A and SP-D levels on comparison and prognosis of idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

Idiopathic pulmonary fibrosis (IPF) has a poor prognosis in general; however, it is heterogeneous to detect relative biomarkers for predicting the disease progression. Serum biomarkers can be conveniently collected to detect and help to differentially diagnose IPF and predict IPF prognosis. This meta-analysis aimed to evaluate the use of serum surfactant proteins A and D (SP-A and SP-D) for differential diagnosis and prognosis of IPF. Relevant articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases and reviewed by 2 independent readers. Standard mean difference (SMD) and 95% confidence interval (CI) were calculated to assess the difference in serum levels of SP-A/D among patients with IPF, when compared to patients with non-IPF interstitial lung disease (ILD), pulmonary infection, and healthy control. Hazard ratio (HR) and 95% CI were used to compare the relative risk of mortality. Twenty-one articles (totalling 1289 IPF patients) were included in final meta-analysis. Serum SP-A levels were significantly higher in patients with IPF than in patients with non-IPF ILD (SMD: 1.108 [0.584, 1.632], P < .001), or pulmonary infection (SMD: 1.320 [0.999, 1.640], P < .001) and healthy controls (SMD: 2.802 [1.901, 3.702], P < .001). There was no significant difference in serum SP-D levels between patients with IPF and those with non-IPF ILD patients (SMD: 0.459 [-0.000, 0.919], P = .050). Serum SP-D levels were significantly higher in patients with IPF than in patients with pulmonary infection (SMD: 1.308 [0.813, 1.803], P < .001) and healthy controls (SMD: 2.235 [1.739, 2.731], P < .001). Risk of death in patients with IPF and elevated serum SP-A was increased 39% compared to patients with low SP-A groups. Elevated SP-D increased risk by 111% when compared to low SP-D. In acute exacerbation of IPF, serum SP-A/D were higher than those in stable stage. The comparisons and prognosis might be different in Asian and Caucasian patients. Serum SP-A/D detection might be useful for differential diagnosis and prediction of survival in patients with IPF.