Idiopathic Pulmonary Fibrosis Cohort Research Articles

P070 Rheum to Empower: Home Spirometry and Oximetry Monitoring in Connective Tissue Related Interstitial Lung Disease

Abstract Background/Aims Interstitial lung disease (ILD) is a common cause of morbidity and mortality in connective tissue diseases (CTDs). Distinct challenges arise for individuals with impairments from rheumatic diseases, especially when coupled with respiratory symptoms. While home spirometry monitoring is valuable for patients with idiopathic pulmonary fibrosis (IPF), its applicability in CTD related ILD (CTD-ILD) is relatively unexplored. This study examines the feasibility and acceptability of home spirometry and oximetry monitoring in CTD-ILD patients compared with those with IPF. Methods Patients with CTD-ILD and IPF were recruited prospectively in a tertiary hospital. A portable handheld spirometer (MIR Spirobank Smart) and a Nonin finger oximeter linked to a smartphone app were provided, and patients were educated on its use. Spirometry and oximetry results were collated. At six months, a survey was conducted to assess patients’ perception of home monitoring. Results Fourty-one patients with CTD-ILD and 51 with IPF were recruited. The median ages were 66 and 71 years respectively (Table 1). 2946 FVC and 2787 oximetry readings were captured in the CTD-ILD cohort compared with 4984 FVC and 4778 oximetry readings in the IPF cohort. Among the 41 patients, 12 experienced Raynaud’s phenomenon. Only 7.32% (3/41) of CTD-ILD patients required an ear oximeter due to inaccurate oxygen saturation measurement caused by Raynaud’s phenomenon. Among the CTD-ILD cohort, 16.67% (6/36) experienced difficulty using the devices due to hand problems, while none of the IPF cohort encountered such issues. In the survey, patients reported barriers to long-term remote monitoring usage included forgetting to use, coughing or breathlessness. Less than one-third of patients indicated that spirometry and oximetry results contributed to health anxiety. A majority of patients found home monitoring useful and insightful, and would recommend this to others. Conclusion Our findings suggest the practicality of remotely monitoring FVC and oximetry in CTD-ILD patients, even with challenges like Raynaud’s phenomenon and impaired hand function. This not only underscores feasibility but also empowers patients through continuous monitoring despite physical limitations. Incorporating remote monitoring into standard care should be regarded as an essential approach for this understudied population, enhancing both clinical management and patient empowerment. Disclosure W. Ng: Grants/research support; StAR MD Scholarship, ISR Rheumatology Patient Initiative Fund. D. Howard: None. L. Durcan: None. K. Hurley: Grants/research support; Health Research Board, Ireland, Emerging Clinical Scientist Award (ECSA-2020-011).

Quantitative Analysis of Lung Shape in Idiopathic Pulmonary Fibrosis: Insights Into Disease- and Age-Associated Patterns

Rationale and objectivesFibrotic scarring in idiopathic pulmonary fibrosis (IPF) typically develops first in the posterior-basal lung tissue before advancing to involve more of the lung. The complexity of lung shape in the costo-diaphragmatic region has been proposed as a potential factor in this regional development. Intrinsic and disease-related shape could therefore be important for understanding IPF risk and its staging. We hypothesised that lung and lobe shape in IPF would have important differences from controls. Materials and MethodsA principal component (PC) analysis was used to derive a statistical shape model (SSM) of the lung for a control cohort aged > 50 years (N=39), using segmented lung and fissure surface data from CT imaging. Individual patient shape models derived for baseline (N=18) and follow-up (N=16) CT scans in patients with IPF were projected to the SSM to describe shape as the sum of the SSM average and weighted PC modes. Associations between the first four PC shape modes, lung function, percentage of fibrosis (fibrosis%) and pulmonary vessel-related structures (PVRS%), and other tissue metrics were assessed and compared between the two cohorts. ResultsShape was different between IPF and controls (p<0.05 for all shape modes), with IPF shape forming a distinct shape cluster. Shape had a negative relationship with age in controls (p = 0.013), but a positive relationship with age in IPF (p = 0.026). Some features of shape changed on follow-up. Shape in IPF was associated with fibrosis% (p<0.05) and PVRS% (p<0.05). ConclusionQuantitative comparison of lung and lobe shape in IPF with controls of a similar age reveals shape differences that are strongly associated with age and percent fibrosis. The clustering of IPF cohort shape suggests that it could be an important feature to describe disease.

Epidemiology and Prognostic Significance of Cough in Fibrotic Interstitial Lung Disease.

Rationale: Cough is a key symptom in patients with fibrotic interstitial lung disease (ILD). Objective: This study evaluated the prevalence, longitudinal change, associations, and prognostic significance of cough severity in patients with fibrotic ILD. Methods: We included consecutive patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD who completed the 100mm-Cough Severity Visual Analog Scale (VAS) from the prospective multi-center Canadian Registry for Pulmonary Fibrosis. Baseline cough severity and associations with patient demographics and clinical factors were determined. Relationships between baseline cough severity and health outcomes were evaluated. Measurements and Main Results: Patients with IPF (n=1061) had higher median baseline cough severity than those with non-IPF fibrotic ILD (n=2825) [24 vs 20mm, p<0.001], with worse cough associated with gastroesophageal reflux disease for both cohorts. Worse cough severity was independently associated with worse health-related quality of life at baseline, larger annualized decline in DLCO, development of disease progression, and reduced transplant-free survival in both IPF and non-IPF fibrotic ILD cohorts. The IPF cohort (2.2mm, 95% CI 1.6-2.9mm) had larger annualized increments in cough severity compared to the non-IPF fibrotic ILD cohort (1.1mm, 95% CI 0.8-1.4mm; p=0.004). There was no difference in worsening cough over time comparing those receiving and not receiving ILD-targeted therapy or with and without lung function decline. Conclusion: Cough is common in patients with IPF and non-IPF fibrotic ILD, with increasing cough severity over time irrespective of ILD-targeted therapy. Patient-reported cough severity has prognostic implications on health-related quality of life, disease progression, and survival in fibrotic ILD.

Association Between High Levels of Nitrogen Dioxide and Increased Cumulative Incidence of Lung Cancer in Patients with Idiopathic Pulmonary Fibrosis.

Lung cancer is a fatal complication of idiopathic pulmonary fibrosis (IPF) with a poor prognosis. However, the association between individual exposure to air pollutants and lung cancer development in patients with IPF is unknown. This study aimed to assess the effect of individual exposure to nitrogen dioxide (NO2) on lung cancer development in patients with IPF. We enrolled 1085 patients from the IPF cohort (mean age: 65.6 years, male: 80.6%). We estimated individual-level long-term exposures to NO2 at the patient's residential addresses using a national-scale exposure prediction model based on the data from air quality regulatory monitoring stations. To evaluate the association between NO2 levels and lung cancer development in IPF, we used an individual- and area-level covariates adjusted model as our primary model. The estimated average annual NO2 concentration was 23.1 parts per billion (ppb). During a follow-up of 4.3 years (median), 86 patients (7.9%) developed lung cancer. NO2 concentration was associated with lung cancer development in an unadjusted model (hazard ratio [HR], 1.219; p=0.042), while a marginal association was found in the primary model (HR 1.280; p=0.084). When NO2 concentration was divided by the median value (21.0 ppb), exposure to high NO2 levels (≥ 21.0 ppb) was associated with a 2.0-fold increase in the risk of lung cancer development (HR, 2.023; p=0.047) in the primary model. Individual exposure to high NO2 levels may increase the risk of lung cancer development in patients with IPF.

Development of a Novel Biomarker for the Progression of Idiopathic Pulmonary Fibrosis.

The progression of idiopathic pulmonary fibrosis (IPF) is diverse and unpredictable. We identified and validated a new biomarker for IPF progression. To identify a candidate gene to predict progression, we assessed differentially expressed genes in patients with advanced IPF compared with early IPF and controls in three lung sample cohorts. Candidate gene expression was confirmed using immunohistochemistry and Western blotting of lung tissue samples from an independent IPF clinical cohort. Biomarker potential was assessed using an enzyme-linked immunosorbent assay of serum samples from the retrospective validation cohort. We verified that the final candidate gene reflected the progression of IPF in a prospective validation cohort. In the RNA-seq comparative analysis of lung tissues, CD276, COL7A1, CTSB, GLI2, PIK3R2, PRAF2, IGF2BP3, and NUPR1 were up-regulated, and ADAMTS8 was down-regulated in the samples of advanced IPF. Only CTSB showed significant differences in expression based on Western blotting (n = 12; p < 0.001) and immunohistochemistry between the three groups of the independent IPF cohort. In the retrospective validation cohort (n = 78), serum CTSB levels were higher in the progressive group (n = 25) than in the control (n = 29, mean 7.37 ng/mL vs. 2.70 ng/mL, p < 0.001) and nonprogressive groups (n = 24, mean 7.37 ng/mL vs. 2.56 ng/mL, p < 0.001). In the prospective validation cohort (n = 129), serum CTSB levels were higher in the progressive group than in the nonprogressive group (mean 8.30 ng/mL vs. 3.00 ng/mL, p < 0.001). After adjusting for baseline FVC, we found that CTSB was independently associated with IPF progression (adjusted OR = 2.61, p < 0.001). Serum CTSB levels significantly predicted IPF progression (AUC = 0.944, p < 0.001). Serum CTSB level significantly distinguished the progression of IPF from the non-progression of IPF or healthy control.

Neighborhood Health and Outcomes in Idiopathic Pulmonary Fibrosis.

Rationale: Living in a disadvantaged neighborhood has been associated with worse survival in people with idiopathic pulmonary fibrosis (IPF), however, prior studies have only examined the impact of neighborhood health on outcomes in IPF as a composite measure. Objectives: To investigate the association between neighborhood health and disease severity, measured by pulmonary function at presentation, and death in follow-up, with an additional focus on the contributions of the neighborhood's underlying physical and social factors to these outcomes. Methods: In a retrospective study of participants from the University of California, San Francisco, IPF Cohort (2001-2020), geocoded home addresses were matched to the California Healthy Places Index (HPI), a census-tract measure of neighborhood health. The HPI comprises 25 indicators of neighborhood health that are organized into eight physical and social domains, each of which is weighted and summed to provide a composite HPI score. Regression models were used to examine associations between the HPI as a continuous variable, in quartiles, and across each physical and social domain of the HPI (higher values indicate greater advantage) and forced vital capacity (FVC) percent predicted (% predicted), diffusing capacity of the lung for carbon monoxide (DlCO) % predicted, and death, adjusting for demographic and clinical covariates. We also studied the interaction between disease severity at presentation and neighborhood health in our time-to-event models. Results: In 783 participants with IPF, each 10% increase in HPI was associated with a 1% increase in FVC % predicted and DlCO % predicted (95% confidence intervals [CIs] = 0.55, 1.72; and 0.49, 1.49, respectively). This association appeared primarily driven by the economic, education, access, and social HPI domains. We also observed differences in the associations of HPI with mortality depending on disease severity at presentation. In participants with normal to mildly impaired FVC % predicted (⩾70%) and DlCO % predicted (⩾60%), decreased HPI was associated with higher mortality (hazard ratio = 2.91 Quartile 1 vs. Quartile 4; 95% CI = 1.20, 7.05). No association was observed between the HPI and death for participants with moderate to severely impaired FVC % predicted and DlCO % predicted. Conclusions: Living in disadvantaged neighborhoods was associated with worse pulmonary function in participants with IPF and was independently associated with increased mortality in participants with normal to mild physiological impairment at presentation.

Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000-2016 cohort.

The study aimed to investigate comorbidities, major adverse respiratory events, and mortality in patients with idiopathic pulmonary fibrosis (IPF). We established an IPF cohort and a comparative cohort matched for sex, age, and the date of IPF diagnosis. We recorded the most frequent comorbidities, the proportions, and time durations to the episode of major adverse respiratory events and death. Both cohorts were followed up to the end of 2016. We included 921 patients in the IPF cohort and 3,677 individuals in the comparative cohort. Comorbidities associated with IPF included pulmonary hypertension, chronic obstructive pulmonary disease, heart failure, asthma, and gastroesophageal reflux disease. The IPF cohort was more likely to have pneumonia (47.6 vs 12.0%), acute respiratory failure (17.8 vs 4.30%), chronic respiratory failure (4.23 vs 0.63%), and death (36.3 vs 15.0%) than the comparative cohort. The time durations to the first episode of pneumonia, acute respiratory failure, chronic respiratory failure, and death were 2.09 ± 2.98, 3.12 ± 3.62, 3.20 ± 4.03, and 3.27 ± 3.03 years in the IPF cohort. In conclusion, patients with IPF had significant comorbidities, particularly pulmonary and cardiovascular comorbidities. The duration from diagnosis to the major adverse respiratory events or death was short.

Pulmonary vessel volume in idiopathic pulmonary fibrosis compared with healthy controls aged > 50 years

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive fibrosing interstitial pneumonia with an associated irreversible decline in lung function and quality of life. IPF prevalence increases with age, appearing most frequently in patients aged > 50 years. Pulmonary vessel-like volume (PVV) has been found to be an independent predictor of mortality in IPF and other interstitial lung diseases, however its estimation can be impacted by artefacts associated with image segmentation methods and can be confounded by adjacent fibrosis. This study compares PVV in IPF patients (N = 21) with PVV from a healthy cohort aged > 50 years (N = 59). The analysis includes a connected graph-based approach that aims to minimise artefacts contributing to calculation of PVV. We show that despite a relatively low extent of fibrosis in the IPF cohort (20% of the lung volume), PVV is 2–3 times higher than in controls. This suggests that a standardised method to calculate PVV that accounts for tree connectivity could provide a promising tool to provide early diagnostic or prognostic information in IPF patients and other interstitial lung disease.

Decreased Survival and Lung Function in Progressive Pulmonary Fibrosis

Background and Objectives: Progressive pulmonary fibrosis (PPF) is a recently described term reserved for patients with fibrotic ILD other than idiopathic pulmonary fibrosis (IPF) with fast clinical deterioration. Here, survival and prognostic biomarkers at the time of diagnosis for PPF are investigated in a fibrotic ILD other than IPF cohort (non-IPF). Materials and Methods: Patients diagnosed during the period of 2012-2018 at the ILD Center of Excellence (St. Antonius Hospital, Nieuwegein, The Netherlands) with a fibrotic ILD were included in this study. The presence of PPF was investigated using the criteria from the updated IPF/PPF guideline during the first year after diagnosis. Logistic regression analysis was used to determine risk factors for PPF. A Kaplan-Meier survival analysis with log-rank test was conducted to analyze survival in patients with and without PPF. Results: This study included 304 non-IPF patients and, for comparison, 379 IPF patients. In non-IPF patients, 146 (46%) fulfilled ≥2 criteria for PPF. These patients had a median transplant-free survival rate of 2.9 ± 0.4 years, which was worse than non-IPF patients without PPF (10.1 ± 1.8 years, p < 0.001). The risk for PPF was increased in patients with FVC < 50% (odds ratio (OR) of 2.50, 95% CI = 1.01-6.17, p = 0.047) or DLCOc ≤ 35% (OR = 2.57, 95% CI = 1.24-5.35, p = 0.011). In the first 3 years after diagnosis, survival in PPF and IPF is the same, while in the following years IPF has a significantly worse survival. Conclusions: The non-IPF cohort with PPF had a significantly worse transplant-free survival compared with the non-IPF cohort without PPF. Independent risk factors for PPF in non-IPF were FVC < 50% and DLCOc ≤ 35%.

Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis.

Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP). Two CT scans 6-36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change. Δ-PPFE associated weakly with ILD and FVC change. 22-26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16-1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00-1.35, p=0.045). Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression.

Unsupervised machine learning identifies predictive progression markers of IPF

ObjectivesTo identify and evaluate predictive lung imaging markers and their pathways of change during progression of idiopathic pulmonary fibrosis (IPF) from sequential data of an IPF cohort. To test if these imaging markers predict outcome.MethodsWe studied radiological disease progression in 76 patients with IPF, including overall 190 computed tomography (CT) examinations of the chest. An algorithm identified candidates for imaging patterns marking progression by computationally clustering visual CT features. A classification algorithm selected clusters associated with radiological disease progression by testing their value for recognizing the temporal sequence of examinations. This resulted in radiological disease progression signatures, and pathways of lung tissue change accompanying progression observed across the cohort. Finally, we tested if the dynamics of marker patterns predict outcome, and performed an external validation study on a cohort from a different center.ResultsProgression marker patterns were identified and exhibited high stability in a repeatability experiment with 20 random sub-cohorts of the overall cohort. The 4 top-ranked progression markers were consistently selected as most informative for progression across all random sub-cohorts. After spatial image registration, local tracking of lung pattern transitions revealed a network of tissue transition pathways from healthy to a sequence of disease tissues. The progression markers were predictive for outcome, and the model achieved comparable results on a replication cohort.ConclusionsUnsupervised learning can identify radiological disease progression markers that predict outcome. Local tracking of pattern transitions reveals pathways of radiological disease progression from healthy lung tissue through a sequence of diseased tissue types.Key Points• Unsupervised learning can identify radiological disease progression markers that predict outcome in patients with idiopathic pulmonary fibrosis.• Local tracking of pattern transitions reveals pathways of radiological disease progression from healthy lung tissue through a sequence of diseased tissue types.• The progression markers achieved comparable results on a replication cohort.

P50 Comparison of the EQ-5D-5L and Aqol-8D in a Cohort of People with Idiopathic Pulmonary Fibrosis in Australia

Idiopathic pulmonary fibrosis (IPF) is a debilitating chronic lung disease with a high symptom burden, which has a substantial impact on health-related quality of life (HRQoL). Our study aimed to assess the performance of the EuroQol five-dimension (EQ-5D-5L) and the Assessment of Quality of Life- eight-dimension (AQoL-8D) questionnaires in measuring HRQoL as utility values (HSUVs) in an Australian IPF cohort.

Comorbidity burden and survival in patients with idiopathic pulmonary fibrosis: the EMPIRE registry study

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) frequently have multiple comorbidities, which may influence survival but go under-recognised in clinical practice. We therefore report comorbidity, antifibrotic treatment use and survival of patients with IPF observed in the multi-national EMPIRE registry.MethodsFor this prospective IPF cohort, demographics, comorbidities, survival and causes of death were analysed. Comorbidities were noted by the treating physician based on the patient’s past medical history or as reported during follow-up. Comorbidities were defined as prevalent when noted at enrolment, or as incident when recorded during follow-up. Survival was analysed by Kaplan–Meier estimates, log-rank test, and Cox proportional hazards models. Hazard ratios (HR) were adjusted for gender, age, smoking status and FVC at enrolment.ResultsA population of 3,580 patients with IPF from 11 Central and Eastern European countries was followed every 6 months for up to 6 years. At enrolment, 91.3% of patients reported at least one comorbidity, whereas more than one-third (37.8%) reported four or more comorbidities. Five-year survival was 53.7% in patients with no prevalent comorbidities, whereas it was 48.4%, 47.0%, 43.8% and 41.1% in patients with 1, 2, 3 and ≥ 4 comorbidities, respectively. The presence of multiple comorbidities at enrolment was associated with significantly worse survival (log-rank test P = 0.007). Adjusted HRs indicate that risk of death was increased by 44% in patients with IPF reporting ≥ 4 comorbidities at baseline compared with no comorbidity (P = 0.021). The relationship between number of comorbidities and decreased survival was also seen in patients receiving antifibrotic treatment (63% of all patients; log-rank test P < 0.001). Comorbidity as cause of death was identified in at least 26.1% of deaths.ConclusionsThe majority of patients with IPF demonstrate comorbidities, and many have comorbidity-related deaths. Increasing numbers of comorbidities are associated with worse survival; and this pattern is also present in patients receiving antifibrotic therapy.

The United States Experience of Lung Transplantation in Recipients with COVID-19 Fibrosis: A UNOS/OPTN Analysis

PurposeCoronavirus Disease 19 (COVID-19) is a novel cause of end-stage fibrotic lung disease. Data has been limited to case series and single center reports with regards to outcomes in this unique cohort of patients. We sought to investigate the largest experience to date in patients with COVID-19 fibrosis (CVF) who underwent lung transplantation.MethodsThe United Network for Organ Sharing (UNOS) database was queried for all adult patients (≥18 years old) who underwent isolated lung transplantation between 2018 and July 2021. Recipients diagnosed with CVF were identified and compared to those with idiopathic pulmonary fibrosis (IPF). The IPF cohort included recipients from 2018, in the pre-COVID era. Baseline demographics, perioperative factors, and 30-day outcomes were examined.ResultsA total of 931 recipients were included in this study, 868 (93.2%) and 63 (6.8%) were IPF and CVF, respectively. IPF recipients were on average older (65 vs. 56 years, p<0.001), white race (83% vs. 51%, p<0.001), and less likely to be male (73% vs. 86%, p=0.04). BMI was similar between the IPF and CVF, 27.6 and 27.2 kg/m2, as was the mean PAP 24 and 21 mmHg. The CVF cohort had lower predicted FVC (32% vs. 47%, p=0.01), and had less tobacco use (36% vs 61%, p<0.001). Mean creatinine level was clinically similar, though statistically higher in the IPF cohort, (0.83 vs 0.64, p<0.001). CVF recipients were on the waitlist for a shorter median duration (10 vs 32 days, p<0.001) with a higher LAS (85 vs 41, p<0.001). Notably, more CVF recipient were be on ECMO at time of listing (29% vs 2%, p<0.001) and require ventilatory support (27% vs. 2%, p<0.001). CVF recipients were more likely to receive a double lung transplantation compared to IPF (83% vs 64%, p=0.002), with similar ischemia times, 5.5 vs 5.1 hrs (p=0.17). Mortality at 30 days was comparable between CVF and IPF (7.0% vs. 2.3%, p=0.09), though 20 patients in the CVF cohort had missing data.ConclusionPatients with end-stage lung disease secondary to CVF are higher acuity, and more likely to require ECMO and ventilatory support as a bridge to lung transplantation. Early mortality, while comparable to non-COVID related fibrotic lung disease, remains almost 3 times higher with CVF. In the era of publicly reported survival outcomes, the transplant community may need to reconsider how we approach this new and devastating diagnosis of CVF.

Genotype-Phenotype Relationships in Inheritable Idiopathic Pulmonary Fibrosis: A Greek National Cohort Study

Background: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients’ characteristics in the Greek national IPF cohort with suspected heritability. Patients and Methods: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed. Results: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis. Conclusion: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease’s genetic “richesse,” complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating “personalized” medical care driven by genotypes in the near future.

Clinical Features, Diagnosis, Management, and Outcomes of Idiopathic Pulmonary Fibrosis in Korea: Analysis of the Korea IPF Cohort (KICO) Registry.

BackgroundThe Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients.MethodsBoth newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015.ResultsA total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-age-physiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.ConclusionIn the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.

A clue for obstructive sleep apnea hidden in tomographic images of idiopathic pulmonary fibrosis patients

Objectives: The most common opinion about apnea/hypopnea formation in restrictive pulmonary diseases is based on decreased lung volumes causing upper airway collapse. This study targets to reveal some evidence for this pathophysiological pathway in patients with idiopathic pulmonary fibrosis (IPF) and obstructive sleep apnea (OSA). Methods: The clinical, demographical, and polysomnographic characteristics of 19 patients with OSA and IPF who underwent all-night polysomnography (PSG) were retrospectively evaluated for investigating the correlations between lung volumes calculated on the images of high-resolution computed tomography (HRCT) and polysomnographic findings. Supine HRCT images performed at the time of diagnosis of IPF were used for the calculation of total lung volume and low attenuation areas of the lung (LAA). The results were compared with the results of the PSG and pulmonary function tests (PFT). Results: The study group comprised 19 patients (3 female, 16 male) with a median apnea-hypopnea index (AHI) of 23.5/h. AHI in this IPF cohort was not correlated with body-mass index, neck circumference, age, or PFT. However, overall AHI and non-rapid eye movement (non-REM) AHI had a trend of positive correlation with LAA. We also showed a positive correlation between the LAA and forced vital capacity (FVC) (r=0.682 and, p = 0.003). Conclusions: The severity of OSAS in IPF patients is well correlated with LAA. This result supports the gravitational and the volumetric effect of the lung in apnea-hypopnea formation.

Pulmonary Rehabilitation in Idiopathic Pulmonary Fibrosis and COPD: A Propensity-Matched Real-World Study

BackgroundThe adherence to and clinical efficacy of pulmonary rehabilitation in idiopathic pulmonary fibrosis (IPF), particularly in comparison with COPD, remains uncertain. The objectives of this real-world study were to compare the responses of patients with IPF with a matched group of patients with COPD undergoing the same supervised, outpatient pulmonary rehabilitation program and to determine whether pulmonary rehabilitation is associated with survival in IPF.Research QuestionDo people with IPF improve to the same extent with pulmonary rehabilitation as a matched group of individuals with COPD, and are noncompletion of or nonresponse to pulmonary rehabilitation, or both, associated with 1-year all-cause mortality in IPF?Study Design and MethodsUsing propensity score matching, 163 patients with IPF were matched 1:1 with a control group of 163 patients with COPD referred for pulmonary rehabilitation. We compared between-group pulmonary rehabilitation completion rates and response. Survival status in the IPF cohort was recorded over 1 year after pulmonary rehabilitation discharge. Cox proportional hazards regression explored the association between pulmonary rehabilitation status and all-cause mortality.ResultsSimilar pulmonary rehabilitation completion rates (IPF, 69%; COPD, 63%; P = .24) and improvements in exercise response were observed in both groups with no significant mean between-group differences in incremental shuttle walk test (ISWT) change (mean, 2 m [95% CI, –18 to 22 m]). Pulmonary rehabilitation noncompletion (hazard ratio [HR], 5.62 [95% CI, 2.24-14.08]) and nonresponse (HR, 3.91 [95% CI, 1.54-9.93]) were associated independently with increased 1-year all-cause mortality in IPF.InterpretationThis real-word study demonstrated that patients with IPF have similar completion rates and magnitude of response to pulmonary rehabilitation compared with a matched group of patients with COPD. In IPF, noncompletion of and nonresponse to pulmonary rehabilitation were associated with increased all-cause mortality. These data reinforce the benefits of pulmonary rehabilitation in patients with IPF.

Gender Differences in Idiopathic Pulmonary Fibrosis: Are Men and Women Equal?

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a male predominance. The aim of the study was to explore gender differences in a well-designed French multicentre prospective IPF cohort (COhorte FIbrose, COFI) with a 5-year follow-up.Methods: Between 2007 and 2010, 236 patients with incident IPF were included in COFI. Gender characteristics were compared using a t-test, Chi-squared test and ANOVA, as appropriate. Survival analyses were performed.Results: Fifty-one (22%) females and 185 (78%) males with an average age at diagnosis of 70.1 ± 9.20 and 67.4 ± 10.9 years, respectively, were included in the cohort. Women were significantly less exposed to tobacco smoke [never n = 32 (62.7%) vs. n = 39 (21.1%), p < 0.001] and to occupational exposure [n = 7 (13.7%) vs. n = 63 (34.1%), p = 0.012]. Baseline forced vital capacity, % of predicted (FVC%) was significantly better in women compare to men (83.0% ± 25.0 v. 75.4% ± 18.7 p = 0.046). At presentation honeycombing and emphysema on CT scan were less common in women [n = 40 (78.4%) vs. n = 167 (90.3%) p = 0.041] and [n = 6 (11.8%) vs. n = 48 (25.9%) p = 0.029], respectively. During follow-up fewer women were transplanted compared to men [n = 1 (1.96%) vs. n = 20 (10.8%) p = 0.039]. Medians of survival were comparable by gender [31 months (CI 95%: 28–40) vs. 40 months (CI 95%: 33–72) p = 0.2]. After adjusting for age and FVC at inclusion, being a woman was not associated to a better survival.Conclusions: Women appear to have less advanced disease at diagnosis, maybe due to less exposure history compare to men. Disease progression and overall survival remains comparable regardless gender, but women have less access to lung transplantation.

Outcomes of Idiopathic Pulmonary Fibrosis Improve with Obesity: A Rural Appalachian Experience.

Obesity can be an independent predictor of fibrosis in tissues, including the liver, heart, and skin. We evaluated a rural Appalachian cohort of idiopathic pulmonary fibrosis (IPF) for its relation to obesity. Using American Thoracic Society 2018 diagnostic guidelines, an IPF cohort was systematically identified at an Appalachian academic medical center (2015-2019). The cohort was categorized in subgroups of body mass index (BMI) <30 or BMI ≥30 kg/m2. Demographics, clinical variables, and treatment details were collected retrospectively and evaluated for their associations with obesity. In our IPF cohort (N = 138), a usual interstitial pneumonia pattern was less prevalent in the obese group (n = 49) relative to the nonobese group (69% vs 85%, respectively). The obese group was younger (mean age 73.27 ± 9.12 vs 77.97 ± 9.59 years) and had a higher prevalence of hypertension (90% vs 72%), hyperlipidemia (83% vs 68%), diabetes mellitus (47% vs 25%), sleep-disordered breathing (47% vs 25%), chronic pain disorders (28% vs 15%), and deep vein thrombosis (19% vs 7%). An increased proportion of obese-IPF patients was seen at a tertiary or an interstitial lung disease center, with more surgical lung biopsies performed and incident diagnosis (ie, within 6 months of presentation) assigned. Only a minority of patients underwent lung transplantation (3.6%), all of them from the obese-IPF subgroup. Approximately 30% of the total IPF cohort died, with a lower mortality observed in the obese group (35% vs 20%, P = 0.017). An increasing BMI predicted a better survival in the total IPF cohort (BMI 25-29.9, 20-24.9, and <20 had mortality rates of 20%, 47%, and 75%, respectively; P < 0.001). Our study represents a first known effort to develop an IPF cohort in a rural Appalachian region. Although they shared an increased burden of comorbidities, the obese subgroup showed less advanced fibrosis with a lower mortality rate relative to nonobese subgroup, suggesting a potential "obesity paradox" in IPF. The study findings significantly advance our understanding of challenges posed by IPF in a rural population that also suffers from an alarming rate of obesity. We highlight the need for the multidisciplinary management of these patients and prospective studies to better define this complex relation.