Idiopathic Pulmonary Fibrosis Patients Research Articles

Timing impact on the initiation of pirfenidone therapy on idiopathic pulmonary fibrosis disease progression

In this editorial, we comment on the article by Lei et al, with a specific focus on the timing of the initiation of the antifibrotic agent pirfenidone (PFD) in the management of idiopathic pulmonary fibrosis (IPF) and its impact on lung function of IPF patients. PFD is an antifibrotic agent that is widely used in the management of IPF in both early and advanced stages. It inhibits various pathways and has antifibrotic, anti-inflammatory, and antioxidant properties. Despite dosage lowering, PFD slowed IPF progression and maintained functional capacity. The 6-min walk distance test indicated that patients tolerated adverse events well, and PFD significantly reduced the incidence of progression episodes and death. Even when a single disease-progression event occurred, continuing PFD treatment had benefits.

Could Hepcidin Be a New Biomarker in Patients with Idiopathic Pulmonary Fibrosis (IPF)?

Objectives: Hepcidin is a biomarker produced by hepatocytes in chronic disease anemia and is known to increase during chronic inflammation. This study compares the hepcidin levels in idiopathic pulmonary fibrosis (IPF) patients and controls, evaluating its relationship with anemia and systemic inflammation in IPF patients. Methods: This study included 82 IPF patients and 31 controls. Hepcidin levels were compared between the two groups. In the IPF group, the hepcidin and anemia parameters were compared between anemic and non-anemic patients. The significance between the hepcidin and systemic inflammation parameters such as Erythrocyte Sedimentation Rate, CRP (C-reactive protein) levels, ferritin levels, and the Systemic Immune–Inflammation Index (SII) was investigated. Erythrocyte Sedimentation Rate, C-reactive protein (CRP) levels, and ferritin levels were measured using automated analyzers. Hepcidin and erythropoietin (EPO) levels were determined using ELISA kits. Results: A significant difference in hepcidin levels was found between the IPF and control groups (37.13 ± 14.92 vs. 25.77 ± 11.25, p < 0.001). No significant difference in hepcidin levels was found between anemic and non-anemic IPF patients (38.25 ± 16.2 vs. 36.7 ± 14.6, p = 0.719). No significant correlation was found between hepcidin levels and anemia parameters (serum iron, ferritin, vitamin B12, serum transferrin, transferrin saturation, total iron-binding capacity, hemoglobin, folate, and erythropoietin) in IPF patients. Despite significant differences in the systemic inflammation parameters (ferritin and CRP) between patients and controls, no significant correlation was found between their hepcidin and systemic inflammation parameters. Conclusions: Our study demonstrates that the hepcidin levels in IPF patients are elevated independently of anemia and systemic inflammation. We propose that hepcidin could be a potential biomarker to be investigated in IPF patients.

Spirotetrahydroisoquinoline-Based Histone Deacetylase Inhibitors as New Antifibrotic Agents: Biological Evaluation in Human Fibroblasts from Bronchoalveolar Lavages of Idiopathic Pulmonary Fibrosis Patients

Spirotetrahydroisoquinoline-Based Histone Deacetylase Inhibitors as New Antifibrotic Agents: Biological Evaluation in Human Fibroblasts from Bronchoalveolar Lavages of Idiopathic Pulmonary Fibrosis Patients

Beneficial Impact of Vaccination Against SARS-CoV-2 on the Mental Health of IPF Patients

Background: Depression and anxiety represent significant comorbidities in idiopathic pulmonary fibrosis (IPF) patients, affecting their quality of life. The COVID-19 pandemic has had an uneven impact on global mental health. The Hospital Anxiety and Depression Scale (HADS) constitutes a validated tool to identify anxiety disorders and depression. The aim of this multicentre study was to evaluate the effect of COVID-19 vaccination on depression and anxiety in IPF patients. Methods: Consecutive IPF patients (median 73.5 years) who are regularly followed-up with were included in the study. Demographics, functional, and clinical were recorded. The HADS score was calculated before and one month after vaccination against COVID-19 in all participants. A Wilcoxon signed ranks test was conducted. Results: A total of 180 IPF patients (median 73.5 years) were included in the study. Among them, 145 patients (81%) received antifibrotic treatment. A significant reduction in HADS, both in anxiety and depression scales, was observed one month after vaccination against SARS-COV-2), independent of age, smoking, lung function impairment, and prior history of depression (p < 0.01). Conclusions: A higher Hospital Anxiety and Depression Scale score was detected before vaccination against COVID-19. It seems that vaccination also offered a beneficial effect on depression and anxiety in IPF patients, independent of age, smoking, lung function impairment, and prior history of depression.

Gene polymorphisms and risk of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

Idiopathic pulmonary fibrosis (IPF) has been widely hypothesized to occur as a result of an interplay between a nexus of environmental and genetic risk factors. However, not much is known about the genetic aspect of this disease. The objective of this review was to identify the genetic polymorphisms associated with the risk of developing IPF. We searched PubMed, EBSCO CINAHL Plus, Web of Science, and Wiley Cochrane Library databases for studies on risk factors of IPF published between March 2000 and November 2023. Studies with an IPF diagnosis based only on the American Thoracic Society and the European Respiratory Society guidelines were included. Thirty-one case-control studies were included with 3997 IPF and 20,925 non-IPF subjects. Two of the studies enrolled biopsy-proven IPF patients; 13 studies diagnosed IPF on the basis of clinical and high-resolution computed tomography (HRCT) findings; and 14 studies diagnosed based on both biopsy and clinical and HRCT findings. 16 studies with MUC5B rs35705950, IL-4 rs2243250, IL-4 rs2070874, and tumor necrosis factor α (TNFα)-308 were eligible for meta-analysis. The allele contrast model (T versus G) for MUC5B rs35705950 revealed statistically significant association of T allele with the risk of IPF [odds ratio (OR) 3.84, 95% confidence interval (CI) 3.20 to 4.61, adjusted p<0.0001), as was the allele contrast model for Asian (OR 2.83, 95% CI 1.51 to 5.32, adjusted p=0.009) and Caucasian (OR 4.11, 95% CI 3.56 to 4.75, adjusted p<0.0001). The allele contrast models for IL-4 rs2243250, IL-4 rs2070874, and TNFα-308 did not demonstrate any significant association with IPF. This review suggests an association of MUC5B rs35705950 T allele with the risk of developing IPF. To our knowledge, this study is the first to aggregate several genetic polymorphisms associated with IPF.

Impact of Pirfenidone on arrhythmic and clinical outcomes in patients with idiopathic pulmonary fibrosis

Abstract Background Atrial fibrosis is an important substrate in atrial fibrillation (AF), particularly in the setting of structural heart disease. Previous study reported that pirfenidone, an antifibrotic agent, was beneficial at reducing myocardial fibrosis. The objective of the present study is to evaluate the effects of pirfenidone on arrhythmic and clinical outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods Our database of patients diagnosed with IPF from 2008 to 2023 was used to obtain echocardiography, electrocardiogram (ECG), and 24hr-holter monitoring data. Inclusion criteria were all IPF patients with/without Pirfenidone. And we compared arrhythmic events including atrial fibrillation, atrial premature complex, atrial tachycardia, ventricular arrhythmia and clinical outcomes according to use of Pirfenidone. Results Among 257 patients with IPF (74.0±8.9 years), 106 (42.1%) patients took Pirfenidone. Difference in the baseline characteristics was not observed. During the median 36-month follow-up, a lower incidence of arrhythmic events (P=0.001) and diastolic dysfunction (P=0.025) was observed in the Pirfenidone group. In univariate analysis, hypertension, coronary artery disease, higher body weight, longer PR interval, QRS duration, and less use of Pirfenidone were associated with arrhythmic events. In multivariate analysis, higher body weight and less Pirfenidone use were independent risk factors for arrhythmic events. Conclusions The use of Pirfenidone was associated with less arrhythmic events and lower diastolic dysfunction compared with no use of Pirfenidone in the long-term follow-up. And obesity was associated with higher incidence of arrhythmic events in IPF patients.

Antifibrotic treatment response comparison of progressive pulmonary fibrosis and idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are two entities categorized as fibrotic lung diseases. With a similar clinical presentation and treatment modalities in many cases, the line differentiating these two diseases may not be evident. Hence, it was aimed herein to evaluate the effectiveness of antifibrotic treatment and the course of fibrotic lung diseases. The study included patients diagnosed with IPF and PPF who were given antifibrotic treatment and followed-up for 12 months at our clinic. At the final follow-up, treatment response and radiological evaluation were investigated via high-resolution computed tomography. Eighty-seven patients were included in the study (57 with IPF and 30 with PPF). Under antifibrotic treatment, there were no statistically significant decreases in the six-minute walking test, forced vital capacity, and diffusing capacity of the lungs for carbon monoxide values at 6 and 12 months posttreatment. The most common side effects were photosensitivity for patients under the pirfenidone regimen, while diarrhea was predominantly observed in the PPF group. Radiological progression was observed in 22.9% of the patients at 12 months posttreatment. Hospitalization requirements were more evident in the PPF group, with at least one hospitalization history present in 60% (n = 18) of the PPF patients compared to 12.3% (n = 7) of the IPF patients. A personalized approach is preferred with similar clinical profiles for both treatment modalities, with specific side effects considered.

Clinical, radiological, and serological assessment of the efficacy and safety of nintedanib compared to pirfenidone in a sample of Iraqi patients with idiopathic pulmonary fibrosis: A retrospective cohort study

This study compares the treatment effects after six months of therapy with nintedanib and pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) by comprehensively analyzing key parameters and establishing the diagnostic performance of two biomarkers, Krebs von den Lungen-6(KL-6) and CC chemokine Ligand-18 (CCL-18), to predict treatment outcomes. In a hospital-based retrospective cohort study, 75 patients diagnosed with IPF were divided into three groups based on their treatment: the newly diagnosed group, which included newly diagnosed IPF patients without receiving any antifibrotic treatment (25 patients), IPF patients on pirfenidone treatment (26 patients), and IPF patients on nintedanib treatment (24 patients). After adjustment for age, sex, body mass index, and baseline values of predicted forced vital capacity (FVCp), there was no significant difference in the rate of changes after 24 weeks of follow-up for FVCp (-0.2 ± 0.6, 0.0 ± 2.3, and 0.8 ± 3.5 ml change after 4, 12, and 24 weeks for pirfenidone) and (-1.7 ± 5.9, 1.0 ± 8.9, and 1.4 ± 9.5 ml change after 4, 12, and 24 weeks for nintedanib). CCL-18 offers a better ability to predict radiological findings than KL-6. Most side effects were minor and included diarrhea, stomach pain, skin rash, and hyperpigmentation. In conclusion, both drugs have demonstrated the capacity to postpone the beginning stages of FVCp decrease and lung function decline. There was little difference between the efficacy of nintedanib and pirfenidone. Both drugs were safe and well tolerated for the treatment of IPF.

The impact of COVID-19 infection on idiopathic pulmonary fibrosis mortality: a systematic review and meta-analysis.

COVID-19 has a negative impact on the survival of respiratory patients, especially those with interstitial lung disease. This review aims to better understand the effect of COVID-19 on patients with idiopathic pulmonary fibrosis (IPF). A systematic search of MEDLINE, PubMed, Embase, and Scopus performed from December 2019 up to July 2024 identified relevant studies. Eligibility criteria included English language, sample size ≥10 patients, COVID-19 infection and outcome measures. Two independent reviewers assessed studies using the Newcastle-Ottawa Scale for bias and extracted data. Meta-analysis employed a random-effects model, and the Grading of Recommendations Assessment, Development and Evaluation assessed evidence quality. Outcomes considered were hospitalization, intensive care unit admission, and mortality. Of the 1541 initially identified articles, 6 high-quality studies were included. Meta-analysis revealed a 34% mortality rate [95% confidence interval (CI): 21-48%], 36% hospitalization rate (95% CI: 10-75%), and 31% ICU admission rate (95% CI: 7-71%) among IPF patients with COVID-19. The certainty of evidence was low or very low due to publication bias and heterogeneity. This study underscores the elevated risk of hospitalization and death in IPF patients with COVID-19, emphasizing the vulnerability of this population. Prompt and tailored care is crucial to mitigate the impact of COVID-19 on IPF patients, necessitating proactive measures, vaccination, and comprehensive management.

Rare variants and survival of patients with idiopathic pulmonary fibrosis.

The clinical course of idiopathic pulmonary fibrosis (IPF) is highly variable and unpredictable, with multiple genetic variants influencing IPF outcomes. Notably, rare pathogenic variants in telomere-related genes are associated with poorer clinical outcomes in these patients. Here we assessed whether rare qualifying variants (QVs) in monogenic adult-onset pulmonary fibrosis (PF) genes are associated with IPF survival. Using polygenic risk scores (PRS), we also evaluated the influence of common IPF risk variants in individuals carrying these QVs. We identified QVs in telomere and non-telomere genes linked to monogenic PF forms using whole-genome sequences (WGS) from 888 Pulmonary Fibrosis Foundation Patient Registry (PFFPR) individuals. We also derived a PRS for IPF (PRS-IPF) from 19 previously published common sentinel IPF variants. Using regression models, we then examined the mutual relationships of QVs and PRS-IPF and their association with survival. Validation of results was sought in WGS from an independent IPF study (PROFILE, n=472), and results from the two cohorts were meta-analyzed. Carriers of QVs in monogenic adult-onset PF genes, representing nearly 1 out of 6 IPF patients, were associated with lower PRS-IPF (Odds Ratio [OR]: 1.79; 95% Confidence Interval [CI]: 1.15-2.81; p=0.010) and shorter survival (Hazard Ratio [HR]: 1.53; 95% CI: 1.12-2.10; p=7.3×10-3). Notably, carriers of pathogenic variants at telomere genes showed the strongest association with survival (HR: 1.76; 95% CI: 1.13-2.76; p=0.013). The meta-analysis of the results showed a consistent direction of effect across both cohorts. We revealed the opposite effects of QVs and PRS-IPF on IPF survival. Thus, a distinct IPF molecular subtype might be defined by QVs in monogenic adult-onset PF genes. Assessing the carrier status for QVs and modelling PRS-IPF promises to further contribute to predicting disease progression among IPF patients.

Real-World Experience in the Clinical Use of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis in Taiwan: A Post-Marketing Surveillance Study.

Idiopathic pulmonary fibrosis (IPF) is a serious, progressive lung disease for which treatments are scarce. Pirfenidone has been approved for the treatment of IPF in Taiwan since 2016. This study aimed to gain a better insight into pirfenidone's real-world safety and effectiveness in adult IPF patients in Taiwan. We conducted a prospective, multicenter, post-marketing surveillance study, and analyzed data from a small sample of 50 IPF patients treated with pirfenidone. Most patients were men, with a mean age of 72.8 years (±10.3). They were in physiology stage I or II with a baseline mean forced vital capacity (FVC) of 2.236 L (73.8% of predicted value). After treatment with pirfenidone, the mean FVC decreased by 0.088 L at week 24 and 0.127 L at week 52. The mean 6 min walk test was 325.5 m at baseline, increased by 8.1 m at week 24, but then decreased by 23.0 m at week 52. These changes from baseline did not reach statistical significance. Pirfenidone prevented worsening of cough but did not stabilize dyspnea. During 52 weeks of treatment, the incidence of total adverse drug reactions was 62.0%, with decreased appetite (32.0%) and pruritis (10.0%) being the most common. The adverse events leading to treatment discontinuation were decreased appetite (8.0%), nausea (4.0%), and respiratory failure (4.0%). No safety concern was raised by the study. Treatment with pirfenidone stabilized both FVC and the subjective symptom of cough in most patients. This post-marketing surveillance study demonstrated that pirfenidone is an effective, safe, and well-tolerated treatment in patients with IPF in Taiwan.

Type 2 innate immunity promotes the development of pulmonary fibrosis in Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS), particularly in types 1 and 4, is characterized by progressive pulmonary fibrosis, a major cause of morbidity and mortality. However, the precise mechanisms driving pulmonary fibrosis in HPS are not fully elucidated. Our previous studies suggested that CHI3L1-driven fibroproliferation may be a notable factor in HPS-associated fibrosis. This study aimed to explore the role of CHI3L1-CRTH2 interaction on ILC2s and explored the potential contribution of ILC2-fibroblast crosstalk in the development of pulmonary fibrosis in HPS. We identified ILC2s in lung tissues from idiopathic pulmonary fibrosis (IPF) and HPS patients. Using bleomycin-challenged wild type (WT) and Hps1-/- mice we observed that ILC2s were recruited and appeared to contribute to fibrosis development in the Hps1-/- mice, with CRTH2 playing a notable role in ILC2 accumulation. We sorted ILC2s, profiled fibrosis-related genes and mediators, and conducted co-culture experiments with primary lung ILC2s and fibroblasts. Our findings suggest that ILC2s may directly stimulate the proliferation and differentiation of primary lung fibroblasts partially through Amphiregulin-EGFR-dependent mechanisms. Additionally, specific overexpression of CHI3L1 in the ILC2 population using the IL-7Rcre driver, which was associated with increased fibroproliferation, indicates that ILC2-mediated, CRTH2-dependent mechanisms might contribute to optimal CHI3L1-induced fibroproliferative repair in HPS-associated pulmonary fibrosis.

Tertiary lymphoid structures and B-cell infiltration are IPF features with functional consequences.

Recent literature has shown the presence of B cells and autoantibodies in idiopathic pulmonary fibrosis (IPF) which would imply the presence of tertiary lymphoid structures (TLS, sites where the immune response is triggered), yet TLS are not considered features of the histological characteristics of IPF. This study aims to quantify the presence, size, and degree of activation of TLS in biopsied and explanted lungs from patients with early- and late-IPF, never treated with antifibrotics, and relate their presence and activity to the clinical course, disease progression, and lung inflammation. Immunohistochestry for B cells and CD4, CD8, and CD45 cells was performed in lung tissue from IPF patients: 18 at diagnosis (early), 39 explanted (end-stage), and 12 smoking controls. TLS activation was assessed by CD40 expression. Spirometry along 31 (12-72) months of follow-up was used to characterize end-stage IPF as slow progressors or rapid progressors. B cells, along with other inflammatory cells, were higher in early- and end-stage IPF than in controls (p < 0.001). In rapid progressors, all inflammatory cells were higher than in slow progressors (p < 0.05). TLS were present in 100% of early- and end-stage IPF and in 50% of controls. In end-stage IPF, the TLS area and activation score were higher than in early IPF (p < 0.0001; p = 0.005) and controls (p < 0.04; p < 0.002). TLS activation score correlated with FVC decline during follow-up in rapid progressors (r = 0.73; p = 0.007) but not in slow progressors. A prominent B-cell infiltration, along with the presence of TLS, the activity of which correlates with FVC decline, is an important component of IPF from the beginning of the disease, likely playing an important role on its mechanism and progression.

Referral to pulmonary rehabilitation and palliative care services in people with idiopathic pulmonary fibrosis in England, 2010–2019

The benefits of pulmonary rehabilitation (PR) and palliative care (PC) as non-pharmacological therapies for people with idiopathic pulmonary fibrosis (IPF) are increasingly being recognised but in the UK the proportion of people with this life-limiting condition who are referred to such services is thought to be low. This retrospective cohort study aimed to describe trends in referrals to PR and PC services among people with IPF over a 10-year period and to identify factors associated with non-referral. Our study cohort was drawn from the UK’s pseudonymised Clinical Practice Research Datalink (CPRD) Aurum primary care database and comprised 17,071 individuals diagnosed with IPF between 2010 and 2019. While 12.0% of IPF patients were offered a referral to PR, less than 2% completed a PR programme. Around a fifth (19.4%) received a referral to generic PC support services; however, this is well below reported PC referral rates for lung cancer patients. Moreover, the majority of PC referrals occurred late; among those who died, 31% were referred within a month and 70% within 6 months of death. Referrals to PR and PC had however increased (by around 2–fold and 4-fold, respectively) over the course of the study period. Factors associated with non-referral to PR included female sex, older age and co-diagnosis of dementia; barriers to PC referral included being female or of Asian or Black ethnicity. We also found evidence of regional differences in referrals. These findings confirm that PR and PC service provision for people with IPF across England is suboptimal.

SPP1 induces idiopathic pulmonary fibrosis and NSCLC progression via the PI3K/Akt/mTOR pathway

BackgroundThe prevalence of non-small cell lung cancer (NSCLC) is notably elevated in individuals diagnosed with idiopathic pulmonary fibrosis (IPF). Secreted phosphoprotein 1 (SPP1), known for its involvement in diverse physiological processes, including oncogenesis and organ fibrosis, has an ambiguous role at the intersection of IPF and NSCLC. Our study sought to elucidate the function of SPP1 within the pathogenesis of IPF and its subsequent impact on NSCLC progression.MethodsFour GEO datasets was analyzed for common differential genes and TCGA database was used to analyze the prognosis. The immune infiltration was analyzed by TIMER database. SPP1 expression was examined in human lung tissues, the IPF fibroblasts and the BLM-induced mouse lung fibrosis model. Combined with SPP1 gene gain- and loss-of-function, qRT-PCR, Western blot, EdU and CCK-8 experiments were performed to evaluate the effects and mechanisms of SPP1 in IPF progression. Effect of SPP1 on NSCLC was detected by co-cultured IPF fibroblasts and NSCLC cells.ResultsThrough bioinformatics analysis, we observed a significant overexpression of SPP1 in both IPF and NSCLC patient datasets, correlating with enhanced immune infiltration of cancer-associated fibroblasts in NSCLC. Elevated levels of SPP1 were detected in lung tissue samples from IPF patients and bleomycin-induced mouse models, with partial colocalization observed with α-smooth muscle actin. Knockdown of SPP1 inhibits TGF-β1-induced differentiation of fibroblasts to myofibroblasts and the proliferation of IPF fibroblasts. Conversely, SPP1 overexpression promoted IPF fibroblast proliferation via PI3K/Akt/mTOR pathway. Furthermore, IPF fibroblasts promoted NSCLC cell proliferation and activated the PI3K/Akt/mTOR pathway; these effects were attenuated by SPP1 knockdown in IPF fibroblasts.ConclusionsOur findings suggest that SPP1 functions as a molecule promoting both fibrosis and tumorigenesis, positioning it as a prospective therapeutic target for managing the co-occurrence of IPF and NSCLC.

Quantitative CT-analysis of over aerated lung tissue and correlation with fibrosis extent in patients with idiopathic pulmonary fibrosis

IntroductionThe usual interstitial pneumonia (UIP) pattern, hallmark of idiopathic pulmonary fibrosis (IPF), may induce harmful local overdistension during mechanical ventilation given the juxtaposition of different tissue elasticities. Mechanotransduction, linking mechanical stress and strain to molecular pro-fibrotic pathways, likely contributes to fibrosis progression. Understanding the mechanical forces and aeration patterns in the lungs of IPF patients is crucial for unraveling potential mechanisms of disease progression. Quantitative lung computed tomography (CT) can accurately assess the air content of lung regions, thus informing on zonal distension. This study aims to investigate radiological evidence of lung over aeration in spontaneously breathing UIP patients compared to healthy controls during maximal inspiration.MethodsPatients with IPF diagnosis referred to the Center for Rare Lung Diseases of the University Hospital of Modena (Italy) in the period 2020–2023 who underwent High Resolution Computed Tomography (HRCT) scans at residual volume (RV) and total lung capacity (TLC) using standardized protocols were retrospectively considered eligible. Patients with no signs of lung disease at HRCT performed with the same image acquisition protocol nor at pulmonary function test (PFTs) served as controls. Lung segmentation and quantitative analysis were performed using 3D Slicer software. Lung volumes were measured, and specific density thresholds defined over aerated and fibrotic regions. Comparison between over aerated lung at RV and TLC in the two groups and according to lung lobes was sought. Further, the correlation between aerated lung and the extent of fibrosis was assessed and compared at RV and TLC.ResultsIPF patients (N = 20) exhibited higher over aerated lung proportions than controls (N = 15) both at RV and TLC (4.5% vs. 0.7%, p < 0.0001 and 13.8% vs. 7%, p < 0.0001 respectively). Over aeration increased significantly from RV to TLC in both groups, with no intergroup difference (p = 0.67). Sensitivity analysis revealed significant variations in over aerated lung areas among lobes when passing from RV to TLC with no difference within lobes (p = 0.28). Correlation between over aeration and fibrosis extent was moderate at RV (r = 0.62, p < 0.0001) and weak at TLC (r = 0.27, p = 0.01), being the two significantly different at interpolation analysis (p < 0.0001).ConclusionsThis study provides the first evidence of radiological signs of lung over aeration in patients with UIP-pattern patients when passing from RV to TLC. These findings offer new insights into the complex interplay between mechanical forces, lung structure, and fibrosis and warrant larger and longitudinal investigations.

The Evaluation of the Genetic Polymorphisms of TERT (rs2736100) and MUC5B (rs35705950) in Idiopathic Pulmonary Fibrotic patients

Background: Polymorphisms of the TERT and MUC5B genes have been consistently associated with idiopathic pulmonary fibrosis (IPF) in recent genome-wide genetic studies. In Iraq, we did not find research on the role of these polymorphisms in respiratory disorders, so we conducted this study to evaluate the genetic polymorphisms of TERT (rs2736100) and MUC5B (rs35705950) in IPF patients in Iraq. Method: The current study was a case-control study that included 70 patients who were diagnosed with IPF, in addition to, 70 healthy control groups who had no history or clinical evidence of IPF or asthma. blood samples from participants were obtained for DNA extraction, and T-ARMS-PCR was used to determine genetic polymorphisms of TERT (rs2736100) and MUC5B (rs35705950). Result: Current study showed that the mutant/minor homogenous genotype AA and allele A of TERT (rs2736100) appeared at a higher rate in patients (47% and 87% respectively) compared to control (38.5% and 53% respectively), as this indicator appeared as an effective factor (EF = 0.139 and 0.242 respectively), while the wild/major homogenous genotype CC and allele C were appeared in control at a rate of 38.5% and 50% respectively and in patients at rate 23% and 50% respectively. The results of MUC5B (rs35705950) G/T polymorphism showed that the mutant/minor TT genotype and T allele were associated with the occurrence of the disease (EF = 0.177 and 0.192 respectively) while the wild /major GG genotype and G allele appeared as a protective factor (PF= 0.243 and 0.375 respectively) for the control group. Moreover, most of the smoking patients were carriers of the mutant homogenous genotypes of TERT (rs2736100) and MUC5B (rs35705950). Conclusion: TERT (rs2736100) and MUC5B (rs35705950) polymorphisms are significantly associated with IPF, especially among smokers patients.

The Prognostic Role of Advanced Lung Cancer Inflammation Index in Patients with Idiopathic Pulmonary Fibrosis

Background: The advanced lung cancer inflammation index (ALI) is an innovative and thorough measure designed to assess both inflammation and nutritional status. It includes parameters such as albumin, body mass index (BMI), and the neutrophil-to-lymphocyte ratio (NLR). This research seeks to evaluate the prognosis of idiopathic pulmonary fibrosis (IPF) patients by integrating both inflammation and nutritional status, distinguishing it from conventional inflammation biomarkers. Methods: This study included 102 patients with IPF. Clinical data were extracted from the patients’ medical records. NLR and ALI scores were calculated based on data collected at the initiation of antifibrotic treatment using the following formulas: Neut/Lym for NLR and albumin × BMI/NLR for ALI. Results: ALI values were assessed across various IPF patient subgroups based on gender–age–physiology (GAP) stages (1, 2, and 3), forced vital capacity (FVC) (median split: &lt;70% vs. ≥70%), diffusing capacity for carbon monoxide (DLCO) (&lt;51% vs. ≥51%), 6-Minute Walk Test (6MWT) (&lt;350 vs. ≥350), and the Charlson comorbidity index (CCI) (≤1 vs. &gt;1). Significant differences in ALI were observed with respect to GAP stages, FVC, DLCO, and 6MWT categories (p = 0.000 for all), but not for CCI categories (p = 0.233). Receiver operating characteristic (ROC) curve analysis revealed that ALI had a sensitivity of 63.6% and a specificity of 98.9% at a threshold of 11.2 (AUC = 0.945, 95% CI 0.892–0.998, p &lt; 0.000). Conclusions: Our findings indicate that ALI levels are significantly associated with disease severity and mortality in IPF patients.

Study of malnutrition in patients with idiopathic pulmonary fibrosis

Background Although the interest in Idiopathic Pulmonary Fibrosis (IPF) has increased in recent years due to the appearance of new therapies however the interest has focused on pulmonary involvement with little concern for systemic manifestations such as the nutritional status abnormalities. Thus, our study assessed the malnutrition prevalence in patients with IPF and the best indicators for the assessment of malnutrition among them. Patients and methods This work was conducted on 110 stable IPF patients who attended the outpatient clinic of Ain Shams University Hospitals from October 2020 to July 2021. Data about the detailed history and nutritional assessment was collected. Results 22.7% and 20.9% were malnourished according to the definition of fat-free mass index (FFMI) and body mass index (BMI), respectively. Most malnourished patients according to low FFMI were female; not using PPI was a significant independent predictors of malnutrition. There was a statistically significant relation between low FFMI and low serum albumin, hemoglobin, and oxygen saturation. Our findings also revealed that measuring BMI and being less than or equal to 22.1 kg/m2 and mid-arm circumference (MAC) less than or equal 28.5 cm is significantly related to low free fat mass index (malnutrition) and increases that risk by 31.63 folds. Conclusion Nearly one-quarter of IPF patients were malnourished and it was found that measuring BMI less than or equal to 22.1 kg/m2 together with MAC less than or equal to 28.5 cm can predict low FFMI and that can be used in our clinical approach.

A STUDY ON PIRFENIDONE VERSUS NINTEDANIB IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS IN A TERTIARY CARE HOSPITAL: A CROSS SECTIONAL STUDY

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic condition with a poor prognosis and have an average life expectancy of 3-4 years. Two antifibrotic treatments have been approved to treat IPF: nintedanib and pirfenidone. These medications lower the decline in lung function and lower the risk of acute respiratory deterioration, which is linked with a high morbidity and death.Individual clinical trials have not been powered to demonstrate mortality decreases, however analysis of pooled data from clinical trials and observational research imply that anti-fibrotic drugs increase life expectancy. This study describes the utility of anti-fibrotic drugs and compare their efficacy. Methods and Materials: This 6 month cross-sectional study conducted at Santhiram Medical College and General Hospital in Nandyal.In patients with IPF , Clinical, functional and radiological data were gathered at baseline and during the follow-up, as per our Center procedure.This study compares and evaluates the efficacy of nintedanib and pirfenidone. A total of 40 patients over the age of 18 with IPF diagnosis were included. Patients under 18 years , those with known fibrosing lung diseases, bronchial asthma, COPD, HIV, Tuberculosis, or other organ failures were excluded. Results: At baseline, IPF patients treated with Pirfenidone had Forced vital capacity(FVC) and Forced expiratory volume at 1 second(FEV1) predicted percentages of 63.57 ± 8.34% and 72.31 ± 4.91%, respectively. In IPF patients treated with Nintedanib, at baseline(time 0), FVC and FEV1 percentages were 60.15±8.82% and 72.31±4.91% respectively. There were no significant variations in FVC and FEV1 percentages at time 0 between patients treated with the two medications (p=0.23,p=0.7,respectively). At 3-month follow-up, patients treated with Pirfenidone had predicted FVC and FEV1 values of 65.73 ± 7.84% and 72.94 ± 4.45%, respectively, whereas patients treated with Nintedanib had predicted valuesof 65.75 ± 7.67% and 72.42 ± 4.45%. At 6-month follow-up, patients on Pirfenidone had predicted FVC and FEV1 values of 66.9 ± 8.72% and 73.5 ± 4.50%, respectively. Nintedanib treatment resulted in 67.7±8.46% and 72.94±4.51% outcomes. Conclusion: our study shown that pirfenidone and nintedanib are equally effective at reducing FVC decline over a 6-month time frame.While nintedanib was slightly more beneficial in lowering FVC decline during the 6-month period. Both drugs were well tolerated, while nintedanib showing good tolerance in the majority of IPF patients.