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.

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. 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.

Asthmatic patients with high serum amyloid A have proinflammatory HDL: Implications for augmented systemic and airway inflammation.

Rationale: Serum amyloid A (SAA) is bound to high-density lipoproteins (HDL) in blood. Although SAA is increased in the blood of patients with asthma, it is not known whether this modifies asthma severity.

Objective: We sought to define the clinical characteristics of patients with asthma who have high SAA levels and assess whether HDL from SAA-high patients with asthma is proinflammatory.

Serum levels of small HDL particles are negatively correlated with death or lung transplantation in an observational study of idiopathic pulmonary fibrosis.

Background: Serum lipoproteins, such as high-density lipoproteins (HDL), may influence disease severity in idiopathic pulmonary fibrosis (IPF). Here, we investigated associations between serum lipids and lipoproteins and clinical end-points in IPF.

Methods: Clinical data and serum lipids were analysed from a discovery cohort (59 IPF subjects, 56 healthy volunteers) and validated using an independent, multicentre cohort (207 IPF subjects) from the Pulmonary Fibrosis Foundation registry.

Does 1-minute walk test predict results of 6-minute walk test in patients with idiopathic pulmonary fibrosis?

Background: The six-minute walk test (6MWT) is a readily available tool used to evaluate functional capacity in patients with idiopathic pulmonary fibrosis (IPF). However, it is often logistically challenging to perform in the context of a busy clinical practice. We sought to investigate if the 1MWT distance (1MWD) predicts the 6MWT distance (6MWD), and if an abbreviated walk could accurately predict outcomes in IPF patients.

Long-term tolerability of phosphodiesterase-5 inhibitors in pulmonary hypertension of sickle cell disease.

Objectives: Sickle cell disease-related pulmonary hypertension (SCD-PH) is a complex disorder with multifactorial contributory mechanisms. Previous trials have evaluated the efficacy of pulmonary arterial hypertension (PAH) therapies in SCD-PH with mixed results. We hypothesized that a subset of patients with right heart catheterization (RHC) confirmed disease may benefit from PAH therapy.

Identifying Clinical and Research Priorities in Sickle Cell Lung Disease. An Official American Thoracic Society Workshop Report.

Pulmonary complications of sickle cell disease (SCD) are diverse and encompass acute and chronic disease. The understanding of the natural history of pulmonary complications of SCD is limited, no specific therapies exist, and these complications are a primary cause of morbidity and mortality. We gathered a multidisciplinary group of pediatric and adult hematologists, pulmonologists, and emergency medicine physicians with expertise in SCD-related lung disease along with an SCD patient advocate for an American Thoracic Society-sponsored workshop to review the literature and identify key unanswered clinical and research questions.

Riociguat use in sickle cell related chronic thromboembolic pulmonary hypertension: A case series.

Adults with sickle cell disease can develop pulmonary hypertension from a multitude of etiologies. Classified as WHO Group 5, there are no therapies approved for the treatment of sickle cell disease-pulmonary hypertension. Thromboembolic disease is prevalent in sickle cell disease and can lead to pulmonary hypertension.

Abnormal Ventilation-Perfusion Scan Is Associated with Pulmonary Hypertension in Sickle Cell Adults.

Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated with early mortality. Chronic thromboembolic PH (CTEPH) is an important complication and contributor to PH in SCD but is likely underappreciated. Guidelines recommend ventilation-perfusion (V/Q) scintigraphy as the imaging modality of choice to exclude CTEPH.

JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies.

Background: Monogenic IFN-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease.

Methods: Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes-associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program.

Spironolactone-induced degradation of the TFIIH core complex XPB subunit suppresses NF-κB and AP-1 signalling.

Aims: Spironolactone (SPL) improves endothelial dysfunction and survival in heart failure. Immune modulation, including poorly understood mineralocorticoid receptor (MR)-independent effects of SPL might contribute to these benefits and possibly be useful in other inflammatory cardiovascular diseases such as pulmonary arterial hypertension.

Methods And Results: Using human embryonic kidney cells (HEK 293) expressing specific nuclear receptors, SPL suppressed NF-κB and AP-1 reporter activity independent of MR and other recognized nuclear receptor partners.

High density lipoproteins and type 2 inflammatory biomarkers are negatively correlated in atopic asthmatics.

Blood eosinophil counts and serum periostin levels are biomarkers of type 2 inflammation. Although serum levels of HDL and apoA-I have been associated with less severe airflow obstruction in asthma, it is not known whether serum lipids or lipoprotein particles are correlated with type 2 inflammation in asthmatics. Here, we assessed whether serum lipids and lipoproteins correlated with blood eosinophil counts or serum periostin levels in 165 atopic asthmatics and 163 nonasthmatic subjects with and without atopy.

A randomized, placebo-controlled, double-blinded, crossover trial of pioglitazone for severe asthma.

The PPAR-γ agonist, pioglitazone, was associated with significant side effects and did not improve the primary outcome measure of the Juniper Asthma Quality of Life Questionnaire (AQLQ) score in severe asthmatics. We conclude that no further studies should be performed with pioglitazone for severe asthma.

Pulmonary artery size as a predictor of outcomes in idiopathic pulmonary fibrosis.

Unlabelled: IPF patients have heightened propensity for pulmonary hypertension, which portends a worse outcome. Presence of pulmonary hypertension may be reflected in an enlarged pulmonary artery. We investigated pulmonary artery size measured on high-resolution computed tomography (HRCT) as an outcome predictor in IPF.

Changes in fatigability following intense aerobic exercise training in patients with interstitial lung disease.

Objective: To determine if, in patients with interstitial lung disease (ILD), fatigue might be lessened after vigorous aerobic exercise.

Methods: 13 physically inactive patients (5 men and 8 women; age 57.2 ± 9.

Serum apolipoprotein A-I and large high-density lipoprotein particles are positively correlated with FEV1 in atopic asthma.

Rationale: Although lipids, apolipoproteins, and lipoprotein particles are important modulators of inflammation, varying relationships exist between these parameters and asthma.

Objectives: To determine whether serum lipids and apolipoproteins correlate with the severity of airflow obstruction in subjects with atopy and asthma.

Methods: Serum samples were obtained from 154 atopic and nonatopic subjects without asthma, and 159 subjects with atopy and asthma.

Cardiorespiratory function before and after aerobic exercise training in patients with interstitial lung disease.

Purpose: To characterize the cardiorespiratory response to exercise before and after aerobic exercise training in patients with interstitial lung disease.

Methods: We performed a clinical study, examining 13 patients (New York Heart Association/World Health Organization Functional class II or III) before and after 10 weeks of supervised treadmill exercise walking, at 70% to 80% of heart rate reserve, 30 to 45 minutes per session, 3 times a week. Outcome variables included measures of cardiorespiratory function during a treadmill cardiopulmonary exercise test, with additional near infrared spectroscopy measurements of peripheral oxygen extraction and bioimpedance cardiography measurements of cardiac output.

Pulmonary artery size as a predictor of pulmonary hypertension and outcomes in patients with chronic obstructive pulmonary disease.

Rationale: The relationship between pulmonary artery size with underlying pulmonary hypertension and mortality remains to be determined in COPD. We sought to evaluate the relationships in a cohort of patients with advanced COPD.

Methods: A retrospective study of advanced COPD patients evaluated between 1998 and 2012 was conducted at a tertiary care center.

Outcomes after hospitalization in idiopathic pulmonary fibrosis: a cohort study.

Objective: The outcomes of patients with idiopathic pulmonary fibrosis (IPF) who undergo hospitalization have not been well characterized. We sought to determine the frequency of all-cause and respiratory-related hospitalizations and to evaluate their impact on the subsequent course and survival of patients with IPF.

Methods: The records of patients with IPF evaluated at a tertiary center were examined for the cause and duration of hospitalization.

Gender and the association of smoking with sleep quantity and quality in American adults.

Smoking and gender are known risk factors for sleep disorders. Studies of samples from Norway and Japan have suggested stronger associations between smoking and disrupted sleep in women; therefore, we examined, gender differences in the association in the U.S.

The influence of alternative instruction on 6-min walk test distance.

Background: The goal of the 6-min walk test (6MWT) is to enable patients to walk "as far as possible" as a measure of their functional ability. The impact of the specific walk instructions on patient 6MWT performance is unknown.

Methods: Patients with pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), and other forms of interstitial lung disease (ILD) were recruited to perform four identical 6MWTs with one differing instructional phrase.