Pulmonary Therapy

Oscillating positive expiratory pressure (OPEP) devices may reduce chronic symptoms in patients with obstructive pulmonary disease (COPD); however, no real-world studies have been performed to evaluate the benefits of these devices. The objective of this study was to measure the rate of early (30-day) moderate-to-severe exacerbations and related costs in COPD patients treated with Aerobika, an OPEP device, vs. a matched control group in a real-world setting. The study utilized data from the QuintilesIMS’ CDM hospital database. COPD patients treated with Aerobika OPEP between 9/2013 and 8/2015 were propensity score matched to COPD patients who did not use any positive expiratory pressure device. Severe exacerbation was defined as a hospital admission with a diagnosis for chronic bronchitis or COPD. Moderate-to-severe exacerbation was defined as a hospitalization or an ED visit with a diagnosis for chronic bronchitis or COPD. Exacerbations and costs were compared between cohorts at 30 days. A generalized linear model (GLM) was used to estimate the marginal effect of Aerobika OPEP on the cost of ED visits and hospitalizations due to COPD exacerbations. A total of 405 Aerobika OPEP patients were matched to 405 controls. At 30 days, 18.5% of subjects using the Aerobika OPEP vs. 25.7% of controls had a moderate-to-severe exacerbation (p = 0.014); 13.8% of subjects with Aerobika OPEP vs. 19.0% of controls had a severe exacerbation (p = 0.046). The mean per patient cost of moderate-to-severe exacerbations and severe exacerbations in the Aerobika OPEP group was significantly lower than controls ($2975 vs. $6065; p = 0.008, and $2838 vs. $5871; p = 0.009, respectively). In the GLM, the per-patient cost of moderate-to-severe exacerbations in the Aerobika OPEP group was 34% lower (p = 0.012) than the control group. Study findings suggest that using Aerobika OPEP as part of a treatment regimen may help reduce ED visits, hospital re-admissions and related costs in COPD patients who have a history of exacerbations.

Hospitalization is an important clinical factor associated with survival and rehospitalization in patients with pulmonary arterial hypertension (PAH). Thus, this study examined treatment patterns before and after hospitalization in the US-specific population. Adult PAH patients in the United States were identified using the Optum® Clinformatics® database from January 1, 2014, to June 30, 2019, and were required to have continuous health plan enrollment for at least 6 months prior to the first (index) hospitalization through at least 90 days post-discharge. Baseline patient characteristics were evaluated from 6 months prior to through the index hospitalization. PAH treatment patterns were examined from 30 days pre-index admission (pre-hospitalization) and 90 days post-index hospital discharge (post-hospitalization), and stratified by therapy type: monotherapy, double- or triple-combination therapy, or no PAH therapy. A total of 3116 hospitalized patients with PAH met selection criteria. The mean age and Charlson comorbidity index score were 68.1 years and 5.1, respectively. In the pre- and post-hospitalization periods (all-cause), respectively, patients prescribed monotherapy were most common (from 64.8% pre- to 51.9% post-hospitalization), followed by patients with no evidence of PAH therapy (from 14.6 to 28.5%). Among PAH-related hospitalizations, patients with monotherapy were also most common (from 60.8% pre- to 49.1% post-hospitalization), followed by patients with no evidence of PAH therapy (from 10.0 to 22.8%). The majority of patients with all-cause hospitalizations (72.8%) had no therapy modification; 20.0% de-escalated therapy (including 15.0% from monotherapy to no therapy) and 6.1% escalated therapy (including 2.2% from no therapy to monotherapy and 3.2% from monotherapy to double or triple therapy). Inpatient admissions did not appear to drive changes in PAH therapy management, as monotherapy predominated, and most patients had no therapy modification within 90 days of a hospitalization. These results warrant future research to understand the reasons behind the limited treatment intensification observed and the impact of post-hospitalization optimization on clinical and economic outcomes.

Components of the hedgehog signaling pathway are upregulated in patients with idiopathic pulmonary fibrosis (IPF). Vismodegib, a small-molecule inhibitor of hedgehog signaling, when used in combination with currently available antifibrotic therapy, may be more efficacious than antifibrotics alone. The objective of this study was to evaluate the safety and tolerability of vismodegib plus pirfenidone in patients with IPF. Twenty-one patients were enrolled in a phase 1b open-label trial to receive vismodegib 150 mg plus pirfenidone 2403 mg/day once daily. Key endpoints were safety, tolerability, and pharmacokinetics. Exploratory endpoints included change from baseline to week 24 in % predicted forced vital capacity (FVC) and University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) scores, as well as pharmacodynamic changes in hedgehog biomarker C-X-C motif chemokine ligand 14 (CXCL14). All patients reported at least one treatment-emergent adverse event (AE), most frequently muscle spasms (76.2%). Serious AEs were reported in 14.3% of patients; one event of dehydration was considered related to vismodegib. One patient died due to IPF progression, unrelated to either treatment. More patients discontinued vismodegib than pirfenidone (42.9% vs. 33.3%, respectively). Changes from baseline to week 24 in % predicted FVC and UCSD-SOBQ scores were within known endpoint variability. In contrast to findings in basal cell carcinoma, vismodegib had no effect on circulating CXCL14 levels. The safety profile was generally consistent with the known profiles of both drugs, with no new safety signals observed in this small cohort. There was no pharmacodynamic effect on CXCL14 levels. Future development of vismodegib for IPF may be limited due to tolerability issues. ClinicalTrials.gov NCT02648048. Plain language summary available for this article. F. Hoffmann-La Roche Ltd. and Genentech, Inc.

Fluid volume management in patients with pulmonary arterial hypertension (PAH) is essential in preventing right ventricular failure. Volume overload may be caused by disease progression, indiscretion of dietary sodium and fluid intake, or medication side effects, and is a frequent complication in patients with PAH. Healthcare professionals (HCPs) who care for patients with PAH have a key role in monitoring, preventing, and managing volume overload. Volume management techniques in patients with PAH include managing diuretic use and electrolyte imbalances, and monitoring fluid retention that can occur from the use of endothelin receptor antagonists or calcium channel blockers. Healthcare providers can create volume management protocols as well as patient educational materials. Patients should be educated to self-monitor their daily weights, incorporate dietary restrictions, and recognize symptoms associated with volume overload. Tools to help HCPs with volume management in patients with PAH are provided in this article. Funding Actelion Pharmaceuticals US, Inc.

Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is a form of mechanical life support that provides full respiratory bypass in patients with severe respiratory failure as a bridge to recovery or lung transplantation. The use of ECMO for respiratory failure and capable centers offering ECMO has expanded over the years, increasing its availability. As VV-ECMO provides an artificial mechanism for oxygenation and decarboxylation of native blood, it allows for an environment in which safer mechanical ventilatory care may be provided, allowing for treatment and resolution of underlying respiratory pathologies. Landmark clinical trials have provided a framework for better understanding patient selection criteria, resource utilization, and outcomes associated with ECMO when applied in settings of refractory respiratory failure. Maintaining close vigilance and management of complications during ECMO as well as identifying strategies post-ECMO (e.g., recovery, transplantation, etc.), are critical to successful ECMO support. In this review, we examine considerations for candidate selection for VV-ECMO, review the evidence of utilizing VV-ECMO in respiratory failure, and provide practical considerations for managing respiratory ECMO patients, including complication identification and management, as well as assessing for the ability to separate from ECMO support and the procedures for decannulation.

The Editors-in-Chief of Pulmonary Therapy have prepared podcasts summarizing their current research, recent highlights from the field, and future predictions. Audio-only versions and the transcripts can be downloaded here: https://doi.org/10.6084/m9.figshare.11938863. Following this is a written summary of the journal’s recent developments and the transcripts from the podcasts.

Fractional exhaled nitric oxide (FeNO) is a non-invasive marker of airway inflammation, and a new portable analyzer (NIOX VERO®) is now available. Our studies aimed to assess the agreement of measurements between NIOX VERO® and a reference device (NIOX MINO®) and assess the reproducibility of NIOX VERO®. Paired FeNO readings were obtained from 112 subjects from both devices to assess agreement and reproducibility. FeNO readings were obtained from 122 subjects using NIOX VERO® to assess inter-operator repeatability. All subjects had a diagnosis of asthma and were aged ≥7 years. Agreement was shown with 90.8% of subjects within tolerance limits for the first valid FeNO measurement. Mean observed paired difference for the first valid FeNO measurement on each device was −4.6 ppb [95% confidence interval (CI) −5.825 to −3.377; < 0.0001]. Weighted Deming Regression Analysis showed a slope of 0.842 (95% CI 0.757, 0.927) and a y-intercept of −0.472 (95% CI −1.999, 1.055). Paired differences were centered close to 0. Intra-subject repeatability of NIOX VERO® was significantly better than NIOX MINO® (p = 0.0112). Further, inter-operator repeatability was achieved with NIOX VERO® with a mean intra-subject variance of 6.61 ± 17.954 ppb (upper 95% CI 9.41) and an estimated standard deviation of 2.57 (upper 95% CI 3.07). The coefficient of variance was 0.066 ± 0.054 (upper 95% CI 0.074). Our findings show that the portable instrument NIOX VERO® is clinically equivalent to NIOX MINO® when used in an asthma population. The NIOX VERO® analyzer gives reproducible, consistent measurements that are well within the technical specifications of the device, showing no observable pattern of a training effect or operator-order effect on FeNO results. Thus, our findings validate the NIOX VERO®. Aerocrine AB, Solna, Sweden.

Asthma is a heterogeneous chronic inflammatory disease of the airways that affects approximately 300 million people worldwide. About 5–10% of all asthmatics suffer from severe or uncontrolled asthma, associated with increased mortality and hospitalization, reduced quality of life, and increased health care costs. In recent years, new treatments have become available, and different asthma phenotypes characterized by specific biomarkers have been identified. Biological drugs are currently indicated for patients with severe asthma that is not controlled with recommended treatments. They are mostly directed against inflammatory molecules of the type 2 inflammatory pathway and are effective at reducing exacerbations, maintaining control over asthma symptoms, and reducing systemic steroid use, which is associated with well-known adverse events. Although biological drugs for severe asthma have had a major impact on the management of the disease, there is still a need for head-to-head comparison studies of biologics and to identify new biomarkers for asthma diagnosis, prognosis, and response to treatment. Identifying novel biomarkers could facilitate the development of therapeutic strategies that are precisely tailored to each patient’s requirements.

M3 antagonist activity was assessed in electrically stimulated human bronchial strips; potency, onset and offset of action of aclidinium, tiotropium and ipratropium were determined. M2 antagonist activity was assessed in electrically stimulated isolated human left atria; duration of action was calculated. Aclidinium demonstrated competitive antagonism at M3 receptors with similar potency to comparators. Onset of action of aclidinium was similar to ipratropium and faster than tiotropium (P < 0.05); duration of action was similar to tiotropium and longer than ipratropium (P < 0.05). At M2 receptors, duration of action of aclidinium was shorter than tiotropium and longer than ipratropium. All antagonists exhibited a shorter duration of action at M2 versus M3 receptors. Aclidinium exhibited kinetic selectivity for human bronchial versus atrial receptors, supporting a favorable cardiovascular safety profile.