Pulmonary Fibrosis Foundation

Efficient distribution of scarce critical care resources is essential to save the most lives in times of crisis. Evidence-based practices and processes enhance clinical decision-making. The objective of these guidelines was to develop evidence-based, rather than expert-based, recommendations for triaging critically ill patients eligible for ICU admission during times of crisis-level shortages in ICU capacity. The American College of Critical Care Medicine Board convened a 21-member multidisciplinary panel, comprising doctors in medicine, nursing, and law; advanced practice providers; respiratory therapists; ethicists; and patient/family representatives. The panel included two expert methodologists specialized in developing evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guidelines development including task force selection and voting. The panel members identified and formulated five fundamental Patient, Intervention, Comparator, and Outcomes questions. The panel conducted a systematic review for each question to identify the best available evidence, analyzed the evidence, and assessed the certainty of the evidence using the GRADE methodology. The GRADE evidence-to-decision framework was used to formulate the recommendations. Good practice statements were included to provide additional guidance. The panel generated one conditional recommendation and five no recommendation statements. Crisis-level shortages significantly disrupt patient care. Despite the role of triage in minimizing adverse outcomes, there is a lack of evidence, as opposed to expert opinion, to guide practice recommendations in the critical clinical scenarios considered by the panel.

Abstract Rationale Sarcoidosis patients are faced with navigating a complex, multisystem medical condition while experiencing impaired quality of life (QOL). This study aims to assess the impact of the Foundation for Sarcoidosis Research (FSR) peer-led support program on patients with sarcoidosis. The study focused on measuring various aspects of sarcoidosis patients’ health understanding and comparing results for those participating in the peer-led support program with the broader cohort. Methods The study utilized the Health Literacy Instrument for Adults validated instrument, as well as FSR-generated questions on demographics and sarcoidosis-specific disease understanding. An online survey was distributed in August 2024 through FSR's community communication channels. Patients who had attended support groups led by FSR-trained peers were self-identified. Metrics included assessments for disease understanding, behaviors, QOL, self-efficacy and therapeutic relationship. Descriptive statistics were generated for various domains and subdomains between patients who attended a peer led support group versus those who had not. A Wilcoxon signed-rank test also examined responses compared to benchmark scores. Results 532 individuals with sarcoidosis completed the survey, 88 (17%) of which reported participation in FSR peer-led support groups. 72% identified as female, 79% white and 13% African American, and 50% lived in a suburban area, with 27% reporting living in urban and 21% rural areas. Those participating in the peer-led groups were more likely to be African American (25% compared to 11%) and to hold a bachelor's degree or higher (69% compared to 58%). Those participating in peer-led groups reported statistically significant (p <.05) higher scores on various aspects of disease understanding, decision-making and therapeutic relationship (Figure 1). Higher domain scores on therapeutic relationship and access to information were reported by African American support-group participants and those with higher household incomes. Conclusions FSR peer-led support groups appear to positively impact participants with sarcoidosis in a variety of domains. Focus groups will reveal whether answers to higher-scored outcomes correlated with peer-led group experience, or if individuals prone to scoring higher in those domains are more likely to choose to engage in a peer-led group. Learnings will be used to strategically expand and improve the FSR peer-led program, as well as enhance outreach to groups underrepresented in current program participants.

Sarcoidosis-associated pulmonary hypertension (SAPH) is an important complication of advanced sarcoidosis. Over the past few years, there have been several studies dealing with screening, diagnosis and treatment of SAPH. This includes the results of two large SAPH-specific registries. A task force was established by the World Association of Sarcoidosis and Other Granulomatous disease (WASOG) to summarise the current level of knowledge in the area and provide guidance for the management of patients. A group of sarcoidosis and pulmonary hypertension experts participated in this task force. The committee developed a consensus regarding initial screening including who should undergo more specific testing with echocardiogram. Based on the results, the committee agreed upon who should undergo right-heart catheterisation and how to interpret the results. The committee felt there was no specific phenotype of a SAPH patient in whom pulmonary hypertension-specific therapy could be definitively recommended. They recommended that treatment decisions be made jointly with a sarcoidosis and pulmonary hypertension expert. The committee recognised that there were significant defects in the current knowledge regarding SAPH, but felt the statement would be useful in directing future studies.

Detailed understanding of longitudinal behavior, response to therapy, and applicable biomarkers for interstitial lung diseases (ILDs) is lacking. There is a need for a large multicenter registry that provides researchers and clinicians access to well-characterized data not limited to patients with idiopathic pulmonary fibrosis. The Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) is a database that collects baseline and longitudinal demographic and clinical information about patients with ILDs in the United States. The objective of this study is to describe the patient population, data collection process, and opportunities for retrospective and prospective research with the PFF-PR. Individuals 18 years or older who had ILD diagnosed and who were seen at PFF-PR centers who provided informed consent were eligible to participate. Baseline and longitudinal demographic, spirometric, radiographic, morbidity, and mortality data are recorded into a secure electronic data capture system. Starting in 2016, the PFF-PR has collected data on 2,003 patients at 42 clinical sites in the United States. At the time of enrollment, the mean age of participants was 68 years old. Most (62%) of participants were male, and 58% had a positive smoking history. The mean forced vital capacity was 69% predicted, and the mean diffusing capacity of the lung for carbon monoxide was 43% predicted. Forty-one percent of patients were using supplemental oxygen, and 39% were on antifibrotic therapy. Reasons for attrition were mostly death or transplant, with low rates of loss to follow-up or withdrawal. The PFF-PR is a large multicenter United States-based registry that provides researchers and clinicians access to well-characterized ILD patient data.

Rationale: Socioeconomic factors are associated with worse disease severity at presentation in sarcoidosis, but the relative importance of socioeconomic variables on morbidity and disease burden has not been fully elucidated.Objectives: To determine the association between income and sarcoidosis outcomes after controlling for socioeconomic and disease-related factors.Methods: Using the Sarcoidosis Advanced Registry for Cures database, we analyzed data from 2,318 patients with sarcoidosis in the United States to determine the effect of income and other variables on outcomes. We divided comorbidities arising after diagnosis into those likely related to steroid use and those likely related to sarcoidosis. We assessed the development of health-related, functional, and socioeconomic outcomes following the diagnosis of sarcoidosis.Measurements and Main Results: In multivariate analysis, low-income patients had significantly higher rates of new sarcoidosis-related comorbidities (<$35,000, odds ratio [OR], 2.4 [1.7-3.3]; $35,000-84,999, OR, 1.4 [1.1-1.9]; and ≥$85,000 [reference (Ref)]) and new steroid-related comorbidities (<$35,000, OR, 1.3 [0.9-2.0]; $35,000-84,999, OR, 1.5 [1.1-2.1]; and ≥$85,000 [Ref]), had lower health-related quality of life as assessed by the Sarcoidosis Health Questionnaire (P < 0.001), and experienced more impact on family finances (<$35,000, OR, 7.9 [4.9-12.7]; $35,000-84,999, OR, 2.7 [1.9-3.9]; and ≥$85,000 [Ref]). The use of supplemental oxygen, need for assistive devices, and job loss were more common in lower income patients. Development of comorbidities after diagnosis of sarcoidosis occurred in 63% of patients and were strong independent predictors of poor outcomes. In random forest modeling, income was consistently a leading predictor of outcome.Conclusions: These results suggest the burden from sarcoidosis preferentially impacts the economically disadvantaged.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown cause with a median survival of only 3 years. Other investigators and we have shown that fibroblasts derived from IPF lungs display characteristics of senescent cells, and that dysregulated activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) correlates with IPF progression. The question of whether STAT3 activation is involved in fibroblast senescence remains unanswered. We hypothesized that inhibiting STAT3 activation after oxidant-induced senescence would attenuate characteristics of the senescent phenotype. We aimed to characterize a model of oxidant-induced senescence in human lung fibroblasts and to determine the effect of inhibiting STAT3 activity on the development of senescence. Exposing human lung fibroblasts to 150 μM hydrogen peroxide (H2O2) resulted in increased senescence-associated β-galactosidase content and expression of p21 and IL-6, all of which are features of senescence. The shift into senescence was accompanied by an increase of STAT3 translocation to the nucleus and mitochondria. Additionally, Seahorse analysis provided evidence of increased mitochondrial respiration characterized by increased basal respiration, proton leak, and an associated increase in superoxide (O2-) production in senescent fibroblasts. Targeting STAT3 activity using the small-molecule inhibitor STA-21 attenuated IL-6 production, reduced p21 levels, decreased senescence-associated β-galactosidase accumulation, and restored normal mitochondrial function. The results of this study illustrate that stress-induced senescence in lung fibroblasts involves the activation of STAT3, which can be pharmacologically modulated.

Rationale: Patient demographic, assessment, and outcome data for interstitial lung diseases (ILD) in real-world settings are lacking. The US-based Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) is collecting such data in a cohort projected to comprise at least 2000 subjects. Methods: The PFF-PR enrolls consenting patients at least 18 years old with ILD, excluding sarcoidosis, LAM, PAP, CF, or amyloidosis. Data collected includes history, examination, pulmonary testing, and chest CTs obtained as part of usual care, and patient reported outcomes. We evaluated the baseline characteristics of the first 1461 participants. Results: Of 1461 participants, 57% had IPF. Non-IPF cases included other idiopathic interstitial pneumonias (11%), collagen vascular/autoimmune disease (17%), hypersensitivity pneumonitis (9%), and other (5%). Multidisciplinary conference was used to confirm diagnosis in 564 (37%) of cases: 331 (40%) of IPF and 233 (37%) of non-IPF cases. Lung biopsy was performed in 286 (34%) of IPF and 271 (43%) of non-IPF subjects. In IPF and non-IPF, respectively, surgical biopsy was most common (n=247 vs 212) compared to transbronchial (n=30 vs 50) or cryobiopsy (n=9 vs 9). The use of immunosuppressive and anti-fibrotic medications differed between IPF and non-IPF subjects. Conclusions: This analysis demonstrates the feasibility and potential output of this multi-institutional collaborative effort.