First ever characterisation of the effects of short telomeres in a Singapore interstitial lung disease cohort.

BACKGROUND: Differences in disease behaviour and genotypes are described in Asian and Western interstitial lung disease (ILD) cohorts. Short leukocyte telomere length (LTL) correlates with poor outcomes in Western ILD cohorts but its significance in Asian populations is unknown. We aim to characterise the burden and clinical implications of short LTL in Singaporean ILD patients. METHODS: Patients diagnosed with ILD at Singapore General Hospital were prospectively recruited and compared against 36 healthy controls. The primary outcome was transplant-free survival. Genomic DNA from peripheral blood was extracted and LTL measured using quantitative polymerase chain reaction assay (qPCR). RESULTS: Amongst 165 patients, 37% had short LTL. There was a higher proportion of combined pulmonary fibrosis and emphysema (CPFE) patients with short LTL (n = 21, 34.4% vs n = 16, 15.4%; p < 0.001). Short LTL patients had reduced survival at 12-, 24- and 36-months and median survival of 24 months (p < 0.001) which remained significant following adjustment for smoking, GAP Stage and radiological UIP pattern (Hazard Ratio (HR), 2.74; 95%CI:1.46, 5.11; p = 0.002). They had increased respiratory-related mortality and acute exacerbation incidences. Despite similar baseline lung function, short LTL patients had a faster decline in absolute forced vital capacity (FVC) of -105.3 (95% CI: 151.4, -59.1) mL/year compared to -58.2 (95% CI: 82.9, -33.6) mL/year (p < 0.001) in normal LTL patients. CONCLUSION: Short LTL correlated with increased mortality and faster lung function decline in our Singaporean ILD cohort with a magnitude similar to that in Western ILD cohorts. Further research is needed to integrate LTL assessment into clinical practice.

Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency.

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's 'feels, functions, survives' criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.

Deep Learning Classification of Usual Interstitial Pneumonia Predicts Outcomes.

Rationale: Computed tomography (CT) enables noninvasive diagnosis of usual interstitial pneumonia (UIP), but enhanced image analyses are needed to overcome the limitations of visual assessment. Objectives: Apply multiple instance learning (MIL) to develop an explainable deep learning algorithm for prediction of UIP from CT and validate its performance in independent cohorts. Methods: We trained an MIL algorithm using a pooled dataset (n = 2,143) and tested it in three independent populations: data from a prior publication (n = 127), a single-institution clinical cohort (n = 239), and a national registry of patients with pulmonary fibrosis (n = 979). We tested UIP classification performance using receiver operating characteristic analysis, with histologic UIP as ground truth. Cox proportional hazards and linear mixed-effects models were used to examine associations between MIL predictions and survival or longitudinal FVC. Measurements and Main Results: In two cohorts with biopsy data, MIL improved accuracy for histologic UIP (area under the curve, 0.77 [n = 127] and 0.79 [n = 239]) compared with visual assessment (area under the curve, 0.65 and 0.71). In cohorts with survival data, MIL-UIP classifications were significant for mortality (n = 239, mortality to April 2021: unadjusted hazard ratio, 3.1; 95% confidence interval [CI], 1.96-4.91; P < 0.001; and n = 979, mortality to July 2022: unadjusted hazard ratio, 3.64; 95% CI, 2.66-4.97; P < 0.001). Individuals classified as UIP positive by the algorithm had a significantly greater annual decline in FVC than those classified as UIP negative (-88 ml/yr vs. -45 ml/yr; n = 979; P < 0.01), adjusting for extent of lung fibrosis. Conclusions: Computerized assessment using MIL identifies clinically significant features of UIP on CT. Such a method could improve confidence in radiologic assessment of patients with interstitial lung disease, potentially enabling earlier and more precise diagnosis.

Deep Learning-based Fibrosis Extent on Computed Tomography Predicts Outcome of Fibrosing Interstitial Lung Disease Independent of Visually Assessed Computed Tomography Pattern.

Rationale: Radiologic pattern has been shown to predict survival in patients with fibrosing interstitial lung disease. The additional prognostic value of fibrosis extent by quantitative computed tomography (CT) is unknown. Objectives: We hypothesized that fibrosis extent provides information beyond visually assessed CT pattern that is useful for outcome prediction. Methods: We performed a retrospective analysis of chest CT, demographics, longitudinal pulmonary function, and transplantation-free survival among participants in the Pulmonary Fibrosis Foundation Patient Registry. CT pattern was classified visually according to the 2018 usual interstitial pneumonia criteria. Extent of fibrosis was objectively quantified using data-driven textural analysis. We used Kaplan-Meier plots and Cox proportional hazards and linear mixed-effects models to evaluate the relationships between CT-derived metrics and outcomes. Results: Visual assessment and quantitative analysis were performed on 979 enrollment CT scans. Linear mixed-effect modeling showed that greater baseline fibrosis extent was significantly associated with the annual rate of decline in forced vital capacity. In multivariable models that included CT pattern and fibrosis extent, quantitative fibrosis extent was strongly associated with transplantation-free survival independent of CT pattern (hazard ratio, 1.04; 95% confidence interval, 1.04-1.05; P < 0.001; C statistic = 0.73). Conclusions: The extent of lung fibrosis by quantitative CT is a strong predictor of physiologic progression and survival, independent of visually assessed CT pattern.

Effects of nintedanib on symptoms in patients with progressive pulmonary fibrosis.

BACKGROUND: Dyspnoea and cough can have a profound impact on the lives of patients with pulmonary fibrosis. We investigated the effects of nintedanib on the symptoms and impact of pulmonary fibrosis in patients with progressive pulmonary fibrosis (PPF) in the INBUILD trial using the Living with Pulmonary Fibrosis (L-PF) questionnaire. METHODS: Patients had a fibrosing interstitial lung disease (ILD) (other than idiopathic pulmonary fibrosis) of >10% extent on high-resolution computed tomography (HRCT) and met criteria for ILD progression within the prior 24 months. Patients were randomised 1:1 to receive nintedanib or placebo. Changes in L-PF questionnaire scores from baseline to week 52 were assessed using mixed models for repeated measures. RESULTS: In total, 663 patients were treated. Compared with placebo, there were significantly smaller increases (worsenings) in adjusted mean L-PF questionnaire total (0.5 versus 5.1), symptoms (1.3 versus 5.3), dyspnoea (4.3 versus 7.8) and fatigue (0.7 versus 4.0) scores in the nintedanib group at week 52. L-PF questionnaire cough score decreased in the nintedanib group and increased in the placebo group (-1.8 versus 4.3). L-PF questionnaire impacts score decreased slightly in the nintedanib group and increased in the placebo group (-0.2 versus 4.6). Similar findings were observed in patients with a usual interstitial pneumonia-like fibrotic pattern on HRCT and in patients with other fibrotic patterns on HRCT. CONCLUSION: Based on changes in L-PF questionnaire scores, nintedanib reduced worsening of dyspnoea, fatigue and cough and the impacts of ILD over 52 weeks in patients with PPF.

Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety.

BACKGROUND: Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients. METHODS: We conducted a single-centre, randomised, double-blinded, placebo-controlled trial in adults with FHP and disease progression. Patients were assigned in a 2:1 ratio to receive either oral pirfenidone (2403 mg/day) or placebo for 52 weeks. The primary end point was the mean absolute change in the per cent predicted forced vital capacity (FVC%). Secondary end points included progression-free survival (PFS, time to a relative decline ≥10% in FVC and/or diffusing capacity of the lung for carbon monoxide (DLCO), acute respiratory exacerbation, a decrease of ≥50 m in the 6 min walk distance, increase or introduction of immunosuppressive drugs or death), change in FVC slope and mean DLCO%, hospitalisations, radiological progression of lung fibrosis and safety. RESULTS: After randomising 40 patients, enrolment was interrupted by the COVID-19 pandemic. There was no significant between-group difference in FVC% at week 52 (mean difference -0.76%, 95% CI -6.34 to 4.82). Pirfenidone resulted in a lower rate of decline in the adjusted FVC% at week 26 and improved PFS (HR 0.26, 95% CI 0.12 to 0.60). Results for other secondary end points showed no significant difference between groups. No deaths occurred in the pirfenidone group and one death (respiratory) occurred in the placebo group. There were no treatment-emergent serious adverse events. CONCLUSIONS: The trial was underpowered to detect a difference in the primary end point. Pirfenidone was found to be safe and improved PFS in patients with FHP. TRIAL REGISTRATION MUMBER: NCT02958917.

Serum antibodies to peptidylarginine deiminase-4 in rheumatoid arthritis associated-interstitial lung disease are associated with decreased lung fibrosis and improved survival.

OBJECTIVE: Interstitial lung disease (ILD) is a leading cause of mortality in rheumatoid arthritis (RA), particularly in those with the usual interstitial pneumonia subtype (RA-UIP). Serum antibodies to peptidylarginine deiminase type 4 (anti-PAD4), particularly a subset that cross-react with PAD3 (PAD3/4XR), have been associated with imaging evidence of ILD. We aimed to determine the specificity of anti-PAD4 antibodies in RA-ILD and to examine associations with markers of ILD severity. METHODS: 48 RA-ILD and 31 idiopathic pulmonary fibrosis (IPF) patients were identified from the National Jewish Health Biobank. RA-ILD subtype was defined by imaging pattern on high-resolution chest computed tomography (CT), and serum was tested for anti-PAD4 and anti-PAD3/4XR antibodies. Antibody prevalence, measures of ILD severity (% predicted forced vital capacity, FVC; % predicted diffusion capacity carbon monoxide, DLCO; quantitative CT fibrosis) and mortality were compared between groups. RESULTS: Anti-PAD4 antibodies were present in 9/48 (19%) subjects with RA-ILD and no subjects with IPF. Within RA-ILD, anti-PAD4 antibodies were found almost exclusively in RA-UIP (89%). Within RA-UIP subjects, % predicted FVC was higher in anti-PAD4+ subjects, and this finding was most strongly associated with anti-PAD3/4XR antibodies. In addition, quantitative CT fibrosis score was lower in anti-PAD4+ RA-UIP subjects, including those with mono-reactive anti-PAD4 antibodies and anti-PAD3/4XR antibodies. Anti-PAD4+ RA-UIP subjects also exhibited decreased mortality. CONCLUSIONS: We demonstrate the presence of serum anti-PAD4 antibodies in a subset of patients with RA-UIP that were notably associated with better lung function, less fibrosis and decreased mortality.

Responsiveness and meaningful change thresholds of the Living with Pulmonary Fibrosis (L-PF) questionnaire Dyspnoea and Cough scores in patients with progressive fibrosing interstitial lung diseases.

BACKGROUND: The Living with Pulmonary Fibrosis (L-PF) questionnaire assesses symptoms and quality of life in patients with fibrosing interstitial lung diseases (ILDs). Its Dyspnoea and Cough domains, whose items' responses are based on a 24-hour recall, have scores ranging from 0 to 100, with higher scores indicating greater symptom severity. We evaluated the ability of these domain scores to detect change and estimated their meaningful change thresholds in patients with progressive fibrosing ILDs. METHODS: The INBUILD trial enrolled subjects with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis. The L-PF questionnaire was completed at baseline and week 52. The responsiveness of the Dyspnoea and Cough scores was evaluated by comparing changes in these scores with 52-week changes in three anchors: forced vital capacity % predicted and two self-reported items, one for global physical health and one for global quality of life. We used a triangulation approach including anchor-based and distribution-based methods to estimate meaningful change thresholds. RESULTS: The analyses included 542 subjects with an L-PF Dyspnoea score at baseline and week 52, and 538 subjects with an L-PF Cough score at baseline and week 52. The L-PF Dyspnoea and Cough scores were responsive to change over 52 weeks. Triangulation of anchor-based and distribution-based estimates resulted in meaningful change thresholds of 6 to 7 points for the L-PF Dyspnoea score and 4 to 5 points for the L-PF Cough score to differentiate subjects who were stable or improved from those who deteriorated. CONCLUSION: These analyses support the responsiveness, one aspect of validity, of the L-PF Dyspnoea and Cough domains scores as measures of symptom severity in patients with progressive fibrosing ILDs. Estimates for meaningful change thresholds in these domain scores may be of value in interpreting the effects of interventions in these patients. TRIAL REGISTRATION NUMBER: NCT02999178.

Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD).

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) and non-IPF, progressive fibrotic interstitial lung diseases (PF-ILD), are associated with a progressive loss of lung function and a poor prognosis. Treatment with antifibrotic agents can slow, but not halt, disease progression, and treatment discontinuation because of adverse events is common. Fibrotic diseases such as these can be mediated by lysophosphatidic acid (LPA), which signals via six LPA receptors (LPA1-6). Signalling via LPA1 appears to be fundamental in the pathogenesis of fibrotic diseases. BMS-986278, a second-generation LPA1 antagonist, is currently in phase 2 development as a therapy for IPF and PF-ILD. METHODS AND ANALYSIS: This phase 2, randomised, double-blind, placebo-controlled, parallel-group, international trial will include adults with IPF or PF-ILD. The trial will consist of a 42-day screening period, a 26-week placebo-controlled treatment period, an optional 26-week active-treatment extension period, and a 28-day post-treatment follow-up. Patients in both the IPF (n=240) and PF-ILD (n=120) cohorts will be randomised 1:1:1 to receive 30 mg or 60 mg BMS-986278, or placebo, administered orally two times per day for 26 weeks in the placebo-controlled treatment period. The primary endpoint is rate of change in per cent predicted forced vital capacity from baseline to week 26 in the IPF cohort. ETHICS AND DISSEMINATION: This study will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles, and local ethical and legal requirements. Results will be reported in a peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT04308681.

Managing Cough in Idiopathic Pulmonary Fibrosis.

In many studies, more than one-half of patients with idiopathic pulmonary fibrosis (IPF) endorse cough. In IPF (as in other conditions), when chronic, cough may be frustrating and lead to significant impairments in quality of life. In patients with IPF, comorbid conditions such as gastroesophageal reflux can cause or contribute to cough; when stemming from IPF itself, chronic cough likely arises from multiple mechanisms including mechanical and neurosensory changes. In this article, we review our approach at attempting to identify causes of chronic cough in patients with IPF; these include gastroesophageal reflux disease or upper airway cough syndrome and IPF itself. We cursorily summarize the current evidence for the treatment of chronic cough in IPF, briefly review data on the treatment of unexplained chronic cough and extrapolate it to the treatment of refractory cough in IPF, but we focus our attention on our approaches to evaluation and management, recognizing that some may not be supported by a robust cache of data.

Phase 2 trial to assess lebrikizumab in patients with idiopathic pulmonary fibrosis.

This phase 2, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of lebrikizumab, an interleukin (IL)-13 monoclonal antibody, alone or with background pirfenidone therapy, in patients with idiopathic pulmonary fibrosis (IPF).Patients with IPF aged ≥40 years with forced vital capacity (FVC) of 40%-100% predicted and diffusing capacity for carbon monoxide of 25%-90% predicted and who were treatment-naïve (cohort A) or receiving pirfenidone (2403 mg·day-1; cohort B) were randomised 1:1 to receive lebrikizumab 250 mg or placebo subcutaneously every 4 weeks. The primary endpoint was annualised rate of FVC % predicted decline over 52 weeks.In cohort A, 154 patients were randomised to receive lebrikizumab (n=78) or placebo (n=76). In cohort B, 351 patients receiving pirfenidone were randomised to receive lebrikizumab (n=174) or placebo (n=177). Baseline demographics were balanced across treatment arms in both cohorts. The primary endpoint (annualised rate of FVC % predicted decline) was not met in cohort A (lebrikizumab versus placebo, -5.2% versus -6.2%; p=0.456) or cohort B (lebrikizumab versus placebo, -5.5% versus -6.0%; p=0.557). In cohort B, a non-statistically significant imbalance in mortality favouring combination therapy was observed (hazard ratio 0.42 (95% CI 0.17-1.04)). Pharmacodynamic biomarkers indicated lebrikizumab activity. The safety profile was consistent with that in previous studies of lebrikizumab and pirfenidone as monotherapies.Lebrikizumab alone or with pirfenidone was not associated with reduced FVC % predicted decline over 52 weeks despite evidence of pharmacodynamic activity. Lebrikizumab was well tolerated with a favourable safety profile. These findings suggest that blocking IL-13 may not be sufficient to achieve a lung function benefit in patients with IPF.

Burden of idiopathic pulmonary fibrosis on patients' emotional well being and quality of life: a literature review.

PURPOSE OF REVIEW: To present an overview of the impact of idiopathic pulmonary fibrosis (IPF) on patients' emotional well being and quality of life (QoL). RECENT FINDINGS: IPF is an interstitial lung disease which causes irreversible, progressive lung scarring in a pathological pattern of usual interstitial pneumonia. The incidence of IPF is increasing at a global level, subjecting an increasing number of people to its high morbidity and risk of mortality. Diagnosis is based on a multidisciplinary team approach and the exclusion of other interstitial lung diseases. Two novel antifibrotic treatments, pirfenidone and nintedanib, were recently approved by regulatory agencies around the globe, thus providing many IPF patients with treatment options for the first time. Several other drugs have entered the investigational pipeline, including many in early-phase or late-phase clinical trials. Given the incurable and progressive nature of IPF, even with antifibrotic therapy, depression and anxiety are common among patients; these and burdensome symptoms of breathlessness, cough and fatigue are factors that impact patients' emotional well being and QoL. In addition to even more effective drugs, there is a need for psychosocial interventions and mental health support strategies focused on improving patients' QoL so they are better equipped to live with this devastating condition. SUMMARY: The current article highlights the effects of IPF on patients' emotional well being and QoL and offers suggestions for strategies to help patients with IPF live as well as possible in their daily lives.

Development and Initial Validation Analyses of the Living with Idiopathic Pulmonary Fibrosis Questionnaire.

Rationale: Several new drugs for idiopathic pulmonary fibrosis (IPF) are in development. Tools are needed to assess whether these drugs benefit patients on outcomes that matter most to them. Health-related quality of life (HRQL) is one such outcome. It is influenced by many factors, but symptoms and their impacts are two strong drivers.Objectives: To develop a questionnaire to assess symptoms, disease impacts, and HRQL specifically for patients with IPF.Methods: Working with the U.S. Food and Drug Administration through the Drug Development Tool Qualification process, focus groups, concept elicitation, and cognitive debriefing interviews were conducted to inform the development of a 44-item pilot questionnaire. The pilot paper-and-pen questionnaire was migrated to an equivalent electronic version and field-tested in a 14-day study. Response data were subjected to psychometric testing, including exploratory factor analysis, item calibration using item response theory models, test-retest reliability, and validity testing.Measurements and Main Results: A total of 125 patients with IPF (62.4% men) completed the longitudinal study. The mean ± SD age of the cohort was 69 ± 7.60 years, and the mean FVC% predicted was 71 ± 20.0. After factor and item analyses, 35 items were retained, and these comprise the two modules (symptoms and impacts) of the Living with IPF (L-IPF) questionnaire. The L-IPF yields five scales demonstrating good psychometric properties, including correlation with concurrently collected FVC% predicted and the ability to discriminate between patients with differing levels of IPF severity.Conclusions: The L-IPF is a new questionnaire that assesses symptoms, disease impacts, and HRQL in patients with IPF.

IgA Antibodies Directed Against Citrullinated Protein Antigens Are Elevated in Patients With Idiopathic Pulmonary Fibrosis.

BACKGROUND: The etiology of idiopathic pulmonary fibrosis (IPF) is unknown. Because it shares genetic, histopathologic, and radiographic features with the fibrosing interstitial lung disease seen in rheumatoid arthritis (RA), the goal of this study was to investigate RA-related autoantibodies in IPF. METHODS: The study included patients with IPF from two separate cohorts at National Jewish Health and Brigham Women's Hospital (n = 181), general population control subjects (n = 160), and control subjects with disease (n = 86 [40 with RA-usual interstitial pneumonia and 46 with hypersensitivity pneumonitis]). Serum was tested for RA-associated antibodies (including IgG and IgA) to citrullinated protein antigens (ACPA). Lung tissue in 11 patients with IPF was examined for ectopic lymphoid aggregates. RESULTS: An increased prevalence of ACPA positivity was found in two separate IPF cohorts. In particular, positivity for IgA-ACPA was increased in these two IPF cohorts compared with general population control subjects (21.3% and 24.8% vs 5.6%; P < .01). Patients with IPF were more likely to be IgA-ACPA-positive than IgG-ACPA-positive (23.2% vs 8.3%; P < .01), whereas patients with RA were more likely to be IgG-ACPA-positive than IgA-ACPA-positive (72.5% vs 52.5%; P = .04). There was a strong correlation between IgA-ACPA level and the number of ectopic lymphoid aggregates on lung histologic examination in IPF (r = 0.72; P = .01). CONCLUSIONS: In this study, IgA-ACPA was elevated in patients with IPF and correlated with lymphoid aggregates in the lung, supporting the theory that IgA-ACPA may play a role in lung disease pathogenesis in a subset of individuals with IPF. Future studies are needed to determine whether this subset of ACPA-positive patients with IPF is distinct from patients with IPF but without antibodies.

Clinical Characteristics and Natural History of Autoimmune Forms of Interstitial Lung Disease: A Single-Center Experience.

OBJECTIVE: To describe the phenotypic characteristics and natural history of patients with autoimmune forms of interstitial lung disease (ILD). METHODS: Retrospective, descriptive, single-center study of patients with autoimmune forms of ILD evaluated between February 2008 and August 2014. All data were extracted from the electronic medical record. Longitudinal changes in forced vital capacity (FVC%) and diffusion capacity for carbon monoxide (DLco%) in percent predicted were analyzed and time-to-event analyses for death were performed using Cox regression. RESULTS: Of the entire cohort (n = 243), systemic sclerosis (SSc)-associated ILD (n = 88, 36%), interstitial pneumonia with autoimmune features (IPAF, n = 56, 23%), rheumatoid arthritis (RA)-associated ILD (n = 42, 17%), and idiopathic inflammatory myopathy (IIM)-associated ILD (n = 26, 11%) were the most common phenotypes. The SSc-ILD, IIM-ILD, and IPAF groups had similar features: average age in the mid-50s, strongly female predominant and more likely to have nonspecific interstitial pneumonia (NSIP). In contrast, RA-ILD patients were older, gender balanced, more likely to be past smokers and were UIP predominant. Adjusted longitudinal lung function was stable during a median follow-up period of nearly 4 years and the independent predictors for death were older age (p = 0.003), male sex (p = 0.019), and lower FVC (p = < 0.001). CONCLUSIONS: The predominant phenotypes of autoimmune ILD were SSc-ILD, IPAF, RA-ILD, and IIM-ILD. In contrast to the other subsets, those with RA-ILD may be older, gender balanced, with more smoking history, and higher proportion of UIP. Longitudinal lung function was stable among the groups and younger age, female gender, and better lung function were associated with improved survival.

Idiopathic pulmonary fibrosis: Educational needs of health-care providers, patients, and caregivers.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with poor quality of life. Debilitating symptoms and the reality of shortened survival impact patients' physical and emotional well-being and constrain the lives of patients' caregivers. This study assessed the informational needs of medical providers who care for patients with IPF, IPF patients themselves, and their caregivers. Tailored surveys were sent electronically to providers, patients with IPF, and caregivers of patients with IPF collected on a rolling basis in March of 2017. Providers answered questions regarding their own informational needs and what information they believed patients needed. Patients and caregivers identified their own informational needs and the perceived needs for each other. About 2636 surveys were sent to providers, including 2041 to physicians, of whom 156 completed it. One hundred sixty patients and 29 caregivers responded to the survey via a link on a website. Eighty-six percent of providers described themselves as physicians who diagnose and treat IPF patients themselves. Providers ranked information on "making the diagnosis of IPF" as their top informational need. Patients and caregivers chose "disease progression/what to expect" as the most important informational need for themselves and for each other. Providers want to make a correct diagnosis when IPF is in the differential diagnosis. Patients and caregivers desire clarity around how IPF will behave over time and what their futures with IPF will look like. Resources for patients and their caregivers should include information on disease natural history in empathically worded, clear, and easily accessible formats.

Resequencing Study Confirms That Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis.

Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. Objectives: To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. Methods: We performed deep targeted resequencing (3.69 Mb of DNA) in cases (n = 3,624) and control subjects (n = 4,442) across genes and regions previously associated with disease. We tested for associations between disease and 1) individual common variants via logistic regression and 2) groups of rare variants via sequence kernel association tests. Measurements and Main Results: Statistically significant common variant association signals occurred in all 10 of the regions chosen based on genome-wide association studies. The strongest risk variant is the MUC5B promoter variant rs35705950, with an odds ratio of 5.45 (95% confidence interval, 4.91-6.06) for one copy of the risk allele and 18.68 (95% confidence interval, 13.34-26.17) for two copies of the risk allele (P = 9.60 × 10-295). In addition to identifying for the first time that rare variation in FAM13A is associated with disease, we confirmed the role of rare variation in the TERT and RTEL1 gene regions in the risk of IPF, and found that the FAM13A and TERT regions have independent common and rare variant signals. Conclusions: A limited number of common and rare variants contribute to the risk of idiopathic pulmonary fibrosis in each of the resequencing regions, and these genetic variants focus on biological mechanisms of host defense and cell senescence.