Hypersensitivity Pneumonitis: Updates in Evaluation, Management, and Ongoing Dilemmas.

Hypersensitivity pneumonitis (HP) is a heterogenous disease entity characterized by an aberrant immune response to inhalational antigens. Disease modification hinges on early antigen remediation with a goal to attenuate immune dysregulation. Disease severity and progression are mediated by an interface between degree, type and chronicity of exposure, genetic predisposition, and biochemical properties of the inducing agent.

Treatment Outcomes for Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Real-World, Multisite Study of the Impact of Immunosuppression on Pulmonary Function Trajectory.

Background: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice.

Research Question: How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD?

Study Design And Methods: Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers.

A Phase IIb Randomized Clinical Study of an Anti-αβ Monoclonal Antibody in Idiopathic Pulmonary Fibrosis.

Treatment options for idiopathic pulmonary fibrosis (IPF) are limited. To evaluate the efficacy and safety of BG00011, an anti-αβ IgG1 monoclonal antibody, in the treatment of patients with IPF. In a phase IIb randomized, double-blind, placebo-controlled trial, patients with IPF (FVC ⩾50% predicted, on or off background therapy) were randomized 1:1 to once-weekly subcutaneous BG00011 56 mg or placebo.

Long-term evaluation of the safety and efficacy of recombinant human pentraxin-2 (rhPTX-2) in patients with idiopathic pulmonary fibrosis (IPF): an open-label extension study.

Background: Recombinant human pentraxin-2 (rhPTX-2) significantly decreased decline in percent predicted forced vital capacity (FVC) and stabilized 6-min walk distance (6MWD) in patients with idiopathic pulmonary fibrosis (IPF) during the 28-week, placebo-controlled, randomized period of the Phase II PRM-151-202 study. Interim (76-week) data from the open-label extension (OLE) demonstrated sustained safety and efficacy with rhPTX-2 treatment. Here, we present the entire long-term OLE safety and efficacy data to 128 weeks.

Diagnosis, course and management of hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a complex and heterogeneous interstitial lung disease (ILD) that occurs when susceptible individuals develop an exaggerated immune response to an inhaled antigen. In this review, we discuss the latest guidelines for the diagnostic evaluation of patients with suspected HP, the importance of identifying patients with fibrotic and progressive disease, and the evidence supporting the drugs commonly used in the treatment of HP. Differential diagnosis of HP can be challenging and requires a thorough exposure history, multidisciplinary discussion of clinical and radiologic data, and, in some cases, assessment of bronchoalveolar lavage lymphocytosis and histopathologic findings.

The spectrum of progressive fibrosis interstitial lung disease: clinical and managed care considerations.

Progressive fibrosing interstitial lung diseases (ILDs) encompass a wide range of diseases, including hypersensitivity pneumonitis, occupational diseases, granulomatous diseases, drug-induced diseases, and idiopathic pneumonitis. Given the vast number of progressive fibrosing ILDs and the disparities in clinical patterns and disease features, understanding their clinical and economic impact presents significant challenges. Historically, treatment options for progressive fibrosing ILDs include anti-inflammatory drugs and immunosuppressive.

Assessment of Optimal Screening Tests for the Detection of an Inflammatory Myositis-associated Interstitial Lung Disease.

Background Interstitial lung disease (ILD) is a common pathologic consequence of the idiopathic inflammatory myopathies, and it may be the initial presentation of autoimmune disease in many cases. There are no well-established guidelines to direct the evaluation of this disease in these cases. This study looked at the utility of four common serologic tests to screen for a myositis-associated ILD.

Myocarditis Causing Premature Ventricular Contractions: Insights From the MAVERIC Registry.

Background: Premature ventricular contractions are a common clinical presentation that drives further diagnostic workup. We hypothesize the presence of underlying inflammation is often unrecognized in these patients with a potential for continued disease progression if not diagnosed and treated early in the disease course.

Methods: This is a single-center, prospective study including 107 patients with frequent symptomatic premature ventricular contractions (>5000/24 h) and no known ischemic heart disease.

Long-term treatment with recombinant human pentraxin 2 protein in patients with idiopathic pulmonary fibrosis: an open-label extension study.

Background: Patients with idiopathic pulmonary fibrosis (IPF) treated with PRM-151, a recombinant human pentraxin 2 protein, in a phase 2 double-blind, randomised controlled trial had significantly reduced decline in percentage of predicted forced vital capacity (FVC) and stabilised 6-min walking distance compared with placebo over a 28-week period. Here we report the 76-week results of an open-label extension study.

Methods: Patients who completed the 28-week double-blind period of the PRM-151-202 trial were eligible to participate in the open-label extension study.

Effect of Recombinant Human Pentraxin 2 vs Placebo on Change in Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis: A Randomized Clinical Trial.

Importance: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Approved therapies do not halt disease progression.

Objective: To determine the effect of recombinant human pentraxin 2 vs placebo on change from baseline to week 28 in mean forced vital capacity (FVC) percentage of predicted value.

Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series.

Objective: To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor-α.

Methods: Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes.

Results: Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.

Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis.

In chronic hypersensitivity pneumonitis (CHP), lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified.

Lovastatin Inhibits Low Molecular Weight Hyaluronan Induced Chemokine Expression via LFA-1 and Decreases Bleomycin-Induced Pulmonary Fibrosis.

Background: Lovastatin has a unique ability to bind Leukocyte Function Antigen-1 (LFA-1), an integrin necessary for the full expression of inflammatory cytokines induced by the low molecular weight form of the extracellular matrix glycosaminoglycan hyaluronan (LMW HA). We hypothesized that lovastatin could inhibit LMW HA inflammatory signals via interaction with LFA-1, and attenuate bleomycin induced pulmonary fibrosis.

Methods: We evaluated the effects of lovastatin, pravastatin, LFA-1 blocking antibodies, and a novel LFA-1 inhibitor LFA 878 on LMW HA induced cytokine production in alveolar macrophages.

Hyaluronan fragments induce IFNβ via a novel TLR4-TRIF-TBK1-IRF3-dependent pathway.

Background: The extracellular matrix plays a critical role in insuring tissue integrity and water homeostasis. However, breakdown products of the extracellular matrix have emerged as endogenous danger signals, designed to rapidly activate the immune system against a potential pathogen breach. Type I interferons play a critical role in the immune response against viral infections.

Surfactant addition and alternating current electrophoretic oscillation during size fractionation of nanoparticles in channels with two or three different height segments.

An array of parallel planar nanochannels containing two or three segments with varying inner heights was fabricated and used for size fractionation of inorganic and biological nanoparticles. A liquid suspension of the particles was simply drawn through the nanochannels via capillary action. Using fluorescently labeled 30 nm polyacrylonitrile beads, different trapping behaviors were compared using nanochannels with 200-45 nm and 208-54-30 nm height segments.

Capillary flow in sacrificially etched nanochannels.

Planar nanochannels are fabricated using sacrificial etching technology with sacrificial cores consisting of aluminum, chromium, and germanium, with heights ranging from 18 to 98 nm. Transient filling via capillary action is compared against the Washburn equation [E. W.

Rheumatoid arthritis-associated interstitial lung disease: diagnostic dilemma.

Interstitial lung disease (ILD) is an increasingly recognized complication of rheumatoid arthritis (RA) contributing to significantly increased morbidity and mortality. Diagnosis can be challenging since patients are unlikely to report dyspnea due to an overall decrease in physical activity with advanced arthritic symptoms. Additionally, infections, drug toxicity, and environmental toxins can mimic ILD, creating significant diagnostic dilemmas for the clinician.

Selective trapping and concentration of nanoparticles and viruses in dual-height nanofluidic channels.

Nanofluidic systems offer advantages for chemical analysis, including small sample volumes, size-selective particle trapping, sample concentration and the ability to separate and detect single molecules. Such systems can be fabricated using planar nanochannels, which rely on standard photolithographic techniques. Nanochannel fluid flow can be driven by capillary action, which benefits from simple injection and reasonably high flow rates.

Electroosmotic flow in vapor deposited silicon dioxide and nitride microchannels.

Electroosmotic flow was studied in thin film microchannels with silicon dioxide and silicon nitride sidewalls formed using plasma-enhanced chemical vapor deposition (PECVD). A sacrificial etching process was employed for channel fabrication allowing for cross-sections with heights of 3 mum, ranging from 2 mum to 50 mum in width. Flow rates were measured for single channels and multichannel electroosmotic pump structures for pH levels ranging from 2.

Thin film electro-osmotic pumps for biomicrofluidic applications.

Electro-osmotic flow (EOF) pumps are attractive for fluid manipulation in microfluidic channels. Open channel EOF pumps can produce high pressures and flow rates, and are relatively easy to fabricate on-chip or integrate with other microfluidic or electrical components. An EOF pump design that is conducive to on-chip fabrication consists of multiple small channel arms feeding into a larger flow channel.

Cholesterol depletion reduces serotonin binding and signaling via human 5-HT(7(a)) receptors.

Lipids, including cholesterol, are critical components of the cell membrane where they are enriched in microdomains, lipid rafts, which organize and concentrate receptors and intracellular proteins involved in signal transduction. The present study examined the effects of cholesterol depletion on serotonin (5-HT) binding and signaling via 5-hydroxytryptamine(7) (5-HT(7)) receptors in stably transfected HeLa cells. Immunohistochemical, ligand-binding and biotinylation experiments demonstrated that the studied cells expressed high levels of 5-HT(7) receptors at their surface with a pharmacological profile resembling 5-HT(7) receptors in native tissue.

Differential agonist-mediated internalization of the human 5-hydroxytryptamine 7 receptor isoforms.

The human 5-hydroxytryptamine 7 (5-HT(7)) serotonin receptor is a class A G-protein coupled receptor that has three isoforms, 5-HT(7(a)), 5-HT(7(b)), and 5-HT(7(d)), which are produced by alternative splicing. The 5-HT(7) receptors are expressed in discrete areas of the brain and in both vascular and gastrointestinal smooth muscle. Central nervous system 5-HT(7) receptors may play a role in mood and sleep disorders.

Serotonergic regulation of membrane potential in developing rat prefrontal cortex: coordinated expression of 5-hydroxytryptamine (5-HT)1A, 5-HT2A, and 5-HT7 receptors.

The developing prefrontal cortex receives a dense serotonergic innervation, yet little is known about the actions of serotonin [5-Hydroxytryptamine (5-HT)] in this region during development. Here, we examined the developmental regulation of 5-HT receptors controlling the excitability of pyramidal neurons of this region. Using whole-cell recordings in in vitro brain slices, we identified a dramatic shift in the effects of 5-HT on membrane potential during the postnatal developmental period.

Congenitally learned helpless rats show abnormalities in intracellular signaling.

Background: Affective disorders and the drugs used to treat them lead to changes in intracellular signaling. We used a genetic animal model to investigate to what extent changes in intracellular signal transduction confer a vulnerability to mood or anxiety disorders.

Methods: Levels of gene expression in a selectively bred strain of rats with a high vulnerability to develop congenitally learned helplessness (cLH), a strain highly resistant to the same behavior (cNLH) and outbred Sprague-Dawley (SD) control animals were compared using quantitative reverse transcription polymerase chain reaction.