Comparative Effectiveness of Single Versus Bilateral Lung Transplantation in Dually Listed Recipients: A National Target Trial.

AimTo delineate comorbidities occurring in patients prior to their diagnosis of idiopathic pulmonary fibrosis (IPF). Comorbidity prevalence was compared to age, gender and smoking matched chronic obstructive pulmonary disease (COPD)...

Small airway dysfunction is a pathological component of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), and impulse oscillometry is an easy-to-administer, effort-independent non-invasive test reflecting small airway dysfunction. We aimed to compare the impulse oscillometry (IOS) measurements between COPD and IPF patients and investigate their correlation with severity of both diseases and other conventional parameters. This was a prospective, longitudinal study. We longitudinally evaluated the baseline demographic characteristics, COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scale, Pulmonary Function Test (PFT), Carbon Monoxide Diffusing Capacity (DLCO), Hemogram and Impulse Oscillometry measurements of the patients diagnosed with COPD and IPF. The study included 60 IPF patients and 48 COPD patients. The CAT and mMRC scores were higher in COPD patients. The majority of COPD patients were classified into Category B (46%), while 68% of IPF patients had Stage 1 GAP. The mean FEF 25-75%, which is typically considered to reflect small airway disease, was 93% in IPF patients, while it was significantly lower in COPD patients (29%). Impulse oscillometry measurements were consistent with spirometry parameters. IOS resistance and reactance values were significantly higher in COPD patients than in IPF patients. IOS is advantageous in COPD and IPF patients who cannot exhale due to severe dyspnea, as it is easy to administer and reflects small airway resistance better. Diagnosis of small airway dysfunction may be beneficial in the management of patients with IPF and COPD.

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both debilitating lung diseases which can lead to hypoxemia and pulmonary hypertension (PH). Nuclear Factor of Activated T-cells (NFAT) is a transcription factor implicated in the etiology of vascular remodeling in hypoxic PH. We have previously shown that mice lacking the ability to generate Vasoactive Intestinal Peptide (VIP) develop spontaneous PH, pulmonary arterial remodeling and lung inflammation. Inhibition of NFAT attenuated PH in these mice suggesting a connection between NFAT and VIP. To test the hypotheses that: 1) VIP inhibits NFAT isoform c3 (NFATc3) activity in pulmonary vascular smooth muscle cells; 2) lung NFATc3 activation is associated with disease severity in IPF and COPD patients, and 3) VIP and NFATc3 expression correlate in lung tissue from IPF and COPD patients. NFAT activity was determined in isolated pulmonary arteries from NFAT-luciferase reporter mice. The % of nuclei with NFAT nuclear accumulation was determined in primary human pulmonary artery smooth muscle cell (PASMC) cultures; in lung airway epithelia and smooth muscle and pulmonary endothelia and smooth muscle from IPF and COPD patients; and in PASMC from mouse lung sections by fluorescence microscopy. Both NFAT and VIP mRNA levels were measured in lungs from IPF and COPD patients. Empirical strategies applied to test hypotheses regarding VIP, NFATc3 expression and activity, and disease type and severity. This study shows a significant negative correlation between NFAT isoform c3 protein expression levels in PASMC, activity of NFATc3 in pulmonary endothelial cells, expression and activity of NFATc3 in bronchial epithelial cells and lung function in IPF patients, supporting the concept that NFATc3 is activated in the early stages of IPF. We further show that there is a significant positive correlation between NFATc3 mRNA expression and VIP RNA expression only in lungs from IPF patients. In addition, we found that VIP inhibits NFAT nuclear translocation in primary human pulmonary artery smooth muscle cells (PASMC). Early activation of NFATc3 in IPF patients may contribute to disease progression and the increase in VIP expression could be a protective compensatory mechanism.

Background: While the efficacy of pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) has been well established, emerging evidence also suggests its benefit in idiopathic pulmonary fibrosis (IPF). However, the differences and similarities between how PR affects diseases with different physiologies remain unknown. Objective: This study aimed to compare the efficacy of PR in COPD and IPF patients by performing multifactorial evaluation with various exercise capacity measurements, and dyspnea and health-related quality of life (QoL) assessment. Methods: Twenty-two IPF patients (%vital capacity: 72%) and 27 COPD patients (%forced expiratory volume1: 43%) were recruited. Subjects who completed a 10-week outpatient PR program were analyzed. We assessed five exercise capacity indicators (6-minute walking distance, incremental shuttle walking distance, endurance time, peak work rate, and peak values for oxygen uptake [peak VO2]), dyspnea (Baseline Dyspnea Index: BDI), and health-related QoL (St. George's Respiratory Questionnaire: SGRQ) at baseline and immediately following completion of the PR program. Results: After 10 weeks of PR, all exercise capacity measurements, except VO2, as well as BDI and SGRQ score improved significantly (p<0.05) in both disease groups. The magnitude of the observed changes in each outcome, assessed by the effect size, was comparable between IPF and COPD patients. This was also true for endurance time, the measurement most responsive to PR, with a large effect size. Conclusions: PR can result in comparable improvements in exercise capacity, including endurance time, and dyspnea and HRQoL in both IPF and COPD patients after 10 weeks of exercise training. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 283-289).

From Anti-inflammatory Drugs Through Antifibrotic Agents to Lung Transplantation: A Long Road of Research, Clinical Attempts, and Failures in the Treatment of Idiopathic Pulmonary Fibrosis

<b>Background:</b> Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) have many things in common: triggered by smoking, loss of distal airways since early stage, Club Cell loss. Recently, Single Cell technology identified three Club Cells subtypes differentially altered in COPD suggesting a dysfunctional Club cells differentiation in COPD.&nbsp;However, Club Cells differentiation hasn’t been deeply studied in IPF. <b>Objective:</b> To assess whether Club Cells differentiation in IPF is different from COPD and whether cigarette smoke exposure (CSE) leads to different molecular activation pathways. <b>Methods:</b> ALI cultures from 5 COPD patients and 5 newly diagnosed IPF patients were exposed to cigarette smoke during the differentiation phase to obtain 4 groups: COPD CSE+: COPD CSE- ; IPF CSE+; IPF CSE-.&nbsp;Single Cell was performed to assess the presence and proportion of the 3 Club Cells subtypes in each group. We also compared groups according to morphology, immuno-staining (SCGB3A2, MUC5AC, MUC5B, CCSP), ELISA dosages of cytokines in apical lavages (IL1, IL6, IL8, IL33, IL25, IL17, IL13) and reparation markers ; transcriptome (including identification of transcription factors). <b>Results:</b> At steady state, IPF and COPD ALI cultures contained similar contents of the three different club cell subtypes even though the initial cells were proximally sampled. After CSE exposure, IPF and COPD cells showed different activation states and pro-inflammatory profile suggesting activation of different molecular pathways. <b>Conclusion:</b> Although sharing many features, the airway epithelium of COPD and IPF patients exposed to cigarette smoke seemed not to follow the same activation pathways.

BackgroundOur study examined whether prevalent and incident comorbidities are increased in idiopathic pulmonary fibrosis (IPF) patients when compared to matched chronic obstructive pulmonary disease (COPD) patients and control subjects without IPF or COPD.MethodsIPF and age, gender and smoking matched COPD patients, diagnosed between 01/01/1997 and 01/01/2019 were identified from the Clinical Practice Research Datalink GOLD database multiple registrations cohort at the first date an ICD-10 or read code mentioned IPF/COPD. A control cohort comprised age, gender and pack-year smoking matched subjects without IPF or COPD. Prevalent (prior to IPF/COPD diagnosis) and incident (after IPF/COPD diagnosis) comorbidities were examined. Group differences were estimated using a t-test. Mortality relationships were examined using multivariable Cox proportional hazards adjusted for patient age, gender and smoking status.ResultsAcross 3055 IPF patients, 38% had 3 or more prevalent comorbidities versus 32% of COPD patients and 21% of matched control subjects. Survival time reduced as the number of comorbidities in an individual increased (p < 0.0001).In IPF, prevalent heart failure (Hazard ratio [HR] = 1.62, 95% Confidence Interval [CI]: 1.43–1.84, p < 0.001), chronic kidney disease (HR = 1.27, 95%CI: 1.10–1.47, p = 0.001), cerebrovascular disease (HR = 1.18, 95%CI: 1.02–1.35, p = 0.02), abdominal and peripheral vascular disease (HR = 1.29, 95%CI: 1.09–1.50, p = 0.003) independently associated with reduced survival. Key comorbidities showed increased incidence in IPF (versus COPD) 7–10 years prior to IPF diagnosis.InterpretationThe mortality impact of excessive prevalent comorbidities in IPF versus COPD and smoking matched controls suggests that multiorgan mechanisms of injury need elucidation in patients that develop IPF.

Pulmonary hypertension is associated with increased post-lung transplant mortality risk in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) and Idiopathic pulmonary fibrosis (IPF) are chronic respiratory diseases with high mortality and global disease burdens. While some risk factors are associated with both diseases, such as advanced age and cigarette smoking, they are pathologically distinct. Metabolomic profiling offers insights into underlying biochemical pathways influenced by genetics and environment factors and has been utilized to understand respiratory disease pathology. In this study, we performed untargeted metabolomic profiling of plasma samples from individuals enrolled in the Trans-Omics for Precision Medicine (TOPMed) initiative as part of the Lung Tissue Research Consortium (LTRC), including 480 COPD, 219 IPF, and 361 control participants. Logistic regression was used to identify metabolites significantly associated with COPD and IPF disease status, adjusting for age, sex, BMI, and smoking status. After correcting for false discovery rate, our analysis revealed that 246 (21.8%) of 1131 metabolites (ORs = 0.31-2.99, Padj = 1.9x10^-8 to 0.05) were associated with COPD status, 136 (12.0%) metabolites (ORs = 0.27-6.5, Padj = 7.0x10^-7 to 0.05) were associated with IPF status, and 48 (4.2%) metabolites (ORs = 0.21-13.12 Padj = 1.4x10-6- 0.05) significantly differed between COPD and IPF disease states. COPD and IPF patients shared common metabolomic dysregulation, spanning 80 (7.1%) metabolites, including triglycerides (lower in cases versus controls), cortisol (lower), and androsterone 3-glucuronide (lower). However, there were also distinct metabolomic features unique to COPD, including sphingomyelins (higher in COPD cases versus controls), (lyso)phosphocholines (lower), carnitines (higher), and caffeine (higher), and features unique to IPF, including 15-HETE (higher in IPF cases versus controls), long-chain polyunsaturated fatty acids (higher), Indole-3-lactic acid (lower), and retinol (lower). We further demonstrated that thyroid hormone, which has been shown to have anti-fibrotic properties in mice, has contrasting directions, with higher levels in COPD patients and lower levels in those with IPF. We sought to determine whether the metabolomic differences in COPD versus IPF were driven by shared genetic loci known to exert opposite directions of effect (FAM13A, DSP, ZKSCAN1, STN1, and CRHR1), however our findings did not support this, suggesting the contrasting pathology of these two respiratory conditions may be environmental in origin. In summary, plasma metabolomic profiling of the LTRC populations revealed novel metabolomic signatures suggesting both shared and distinct pathologies for COPD and IPF, deepening our understanding of disease mechanisms and offering potential avenues for targeted therapeutic interventions.

The coexistence of emphysema and pulmonary fibrosis is known as combined pulmonary fibrosis and emphysema (CPFE). The aim of this study was to compare diaphragmatic motion measured by M-mode ultrasonography of patients with CPFE, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD). Pulmonary function, high-resolution computed tomography (HRCT), and diaphragmatic motion were examined in patients with CPFE (n = 25), IPF (n = 18), and COPD (n = 60), and in healthy controls (n = 21). Diaphragmatic motions were measured on M-mode ultrasonographic images during quiet breathing and deep breathing. There were no significant differences in right or left diaphragmatic motion during quiet breathing among the four groups, whereas differences were significant in right and left motion during deep breathing. Diaphragmatic motion in CPFE patients was the lowest among the four groups. COPD patients, especially those with severe COPD, showed significantly lower diaphragmatic motion than IPF patients or healthy controls. There were no differences in diaphragmatic motion between IPF patients and healthy controls. Right diaphragmatic motions during deep breathing were negatively correlated with emphysema scores (r = -0.606, p < 0.001), but were not correlated with fibrosis scores on HRCT. Diaphragmatic weakness was found in CPFE patients. Emphysema but not fibrosis may be one cause of limited diaphragmatic motion in patients with CPFE. M-mode ultrasonographic evaluation of diaphragmatic motion during deep breathing may be a useful tool in diagnosing CPFE and in discriminating CPFE patients from IPF or COPD patients.

Background: The ongoing global pandemic of COVID-19 has raised concerns about its impact on patients with pre-existing respiratory conditions. Understanding the association between COVID-19 and chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) is crucial for early detection and appropriate management. Studying the prevalence rates of COVID-19 in this specific patient population will contribute to the existing knowledge and inform healthcare strategies for better patient care. The objective of this study is to assess the prevalence of COVID-19 infection in patients who presented with acute exacerbation of asthma, COPD and IPF. Method: This cross-sectional descriptive hospital-based study was conducted at Al-Shaab Teaching Hospital in Sudan and included adult Sudanese patients with exacerbation of asthma, COPD, or IPF who presented in the ER from February 2021 to July 2021. A representative sample of 345 patients was selected using a convenience, non-randomized sampling technique. Data were collected using a structured questionnaire and analyzed using SPSS version 26. Ethical clearance and approval were obtained for the study. Results: The study included 175 (50.7%) patients with asthma, 116 (33.6%) with IPF and 54 (15.7%) with COPD. The overall prevalence of COVID-19 among the patients was 58 (16.8%). Among the three groups, the highest prevalence of COVID-19 was observed in 22 (40.7%) patients with COPD, followed by 16 (13.8%) patients with IPF and 20 (11.4%) asthmatic patients (p value &lt; 0.05). In the asthmatic patients, the most common age groups affected were 25-34 years and 35-44 years, while in COPD and IPF patients, the prevalence was higher among patients aged 55 years and above (p value &lt; 0.05). Additionally, the prevalence of COVID-19 in COPD and IPF patients was significantly higher among males than females (p value &lt; 0.05). Conclusion: The prevalence of COVID-19 among patients with pre-existing respiratory conditions, such as asthma, COPD and IPF, is considerable, with the highest prevalence observed in patients with COPD. Furthermore, this study found that age and gender are associated factors with the prevalence of COVID-19 in these patient populations. These findings contribute to our understanding of the association between COVID-19 and chronic lung diseases, providing valuable information for early detection and appropriate management. The results of this study can inform healthcare strategies and contribute to better patient care in this specific patient population.

Comparison of wait times and mortality for idiopathic pulmonary fibrosis patients listed for single or bilateral lung transplantation

243 Comparison of Two Studies of the Upper Esophageal Sphincter (UES) Assist Device for the Treatment of Extraesophageal Reflux

241 Increased Reflux Severity on Impedance Predicts One-Year Pulmonary Function Decline in Pre-Lung Transplant Patients With Idiopathic Pulmonary Fibrosis

50 VE-Cadherin Is Associated with Primary Graft Dysfunction in Lung Transplant Recipients