Cystic Fibrosis Patients May Need Higher Doses of Antibiotics To Clear Lung Infections

MedicalResearch.com Interview with:

Andrea Hahn, M.D., MS Infectious disease specialist and lead study author Children's National Health System

Dr. Hahn

Andrea Hahn, M.D., MS
Infectious disease specialist and lead study author
Children’s National Health System

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: People who have the genetic disease cystic fibrosis have increased sticky secretions in their lungs that put them at risk for repeated bacterial infections. They often will receive courses of intravenous antibiotics to treat more severe or difficult-to-treat infections associated with decreased lung function. However, not all patients fully recover their lung function after antibiotic treatment, despite directing antibiotic therapy toward the specific bacteria thought to be causing the infection. The goal of this study was to determine if the pharmacokinetics of commonly used antibiotics was associated with recovery of lung function.

First, we found that patients with therapeutic blood levels of beta-lactam antibiotics had better lung recovery than patients with sub-therapeutic levels of these antibiotics.

Second, we found that using higher antibiotic dosing according to Cystic Fibrosis Foundation guidelines was not sufficient to predict which patients would have therapeutically meaningful blood levels of antibiotics. Continue reading

Two Studies Evaluate Monoclonal Antibody Tralokinumab For Asthma

MedicalResearch.com Interview with:

Reynold A. Panettieri, Jr., M.D. Professor of Medicine, Robert Wood Johnson Medical School Vice Chancellor, Clinical & Translational Science Director, Rutgers Institute for Translational Medicine & Science Emeritus Professor of Medicine, University of Pennsylvania Child Health Institute of New Jersey Rutgers, The State University of New Jersey New Brunswick, NJ  08901

Dr. Panettieri

Reynold A. Panettieri, Jr., M.D.
Professor of Medicine, Robert Wood Johnson Medical School
Vice Chancellor, Clinical & Translational Science
Director, Rutgers Institute for Translational Medicine & Science
Emeritus Professor of Medicine, University of Pennsylvania
Child Health Institute of New Jersey
Rutgers, The State University of New Jersey
New Brunswick, NJ  08901

MedicalResearch.com: What is the background for this study?

Response: Severe asthma is characterized by Type 2 inflammation manifested by increases in IL-13, IL-4 and Il-5 levels in the airways that promotes airway hyperresponsiveness and in part irreversible airway obstruction.  These clinical manifestations profoundly increase asthma morbidity and mortality.

To address an unmet therapeutic need, Tralokinumab was developed as a monoclonal antibody targeting soluble IL-13 with the goal of improving lung function and patient reported outcomes while decreasing annual exacerbation rates.  Stratus 1 and 2 represent two identical randomized, double-blind, placebo-controlled, phase 3 clinical trials in severe asthma.  These international trials enrolled approximately 2000 subjects with severe asthma and examined whether Tralokinumab decreased annualized exacerbation rates (AER) as compared with placebo (primary outcome).

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Antifibrotic Drug Stabilized Lung Function For Patients with Idiopathic Pulmonary Fibrosis

MedicalResearch.com Interview with:

Pierre Laurin, CEO Prometic

Pierre Laurin

Pierre Laurin, CEO
Prometic Life Sciences

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by idiopathic pulmonary fibrosis?

Response: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, and ultimately fatal disease characterized by a progressive decline in lung function. It is a specific type of interstitial lung disease in which the small air sacs of the lung, the “alveoli,” gradually become replaced by fibrotic (scar) tissue and is the cause of worsening dyspnea (shortness of breath). The 5-year mortality rate for patients with IPF is estimated to range from 50% to 70%.

Small molecule candidate PBI-4050’s anti-fibrotic activity has been observed in various fibrosis models in different organs: lung, kidney, heart, liver, and pancreas. PBI-4050 has been shown to improve forced vital capacity (FVC) in an open-label Phase 2 study in IPF.

The main objective of this exploratory study was to determine whether treatment with PBI-4050 alters the level of key biomarkers in patients with IPF. Subjects with a confirmed diagnosis of IPF received daily oral doses of 800 mg PBI-4050 with or without nintedanib or pirfenidone for 12 weeks. The biomarkers chosen for measurement can be divided into two main groups: cytokines and matrix metalloproteinases associated with fibrosis and inflammation.

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Tiotropium (Spiriva) Found Beneficial In Early Stages of COPD

MedicalResearch.com Interview with:
Dr Prof Nanshan Zhong
, MD (Edin), FRCS (Edin), FRCP and
Pixin Ran PhD

National Center for Respiratory Diseases, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:    According to the latest research, in 2015, 3.2 million people died from COPD globally, with an increase of 11.6% in mortality compared with that in 1990 (GBD 2015 Chronic Respiratory Disease Collaborators. Lancet Respir Med. 2017,5:691-706). COPD has now become the third leading cause of death worldwide and is estimated to become the disease with the seventh greatest burden worldwide in 2030. In China, the prevalence was 8.2% among people aged 40 years or greater, according to our epidemiological survey in 2007.

Importantly, current international guidelines have been mainly focusing on the management of moderate-to-severe COPD. However, among this patient cohort, the severely impaired lung function can only be reversed to a very limited extent despite the most potent treatment combinations. Patients with more advanced COPD are frequently associated with a significantly higher mortality and incidence of re-hospitalization and disability, which cause tremendous economic burden for both the families and the society. However, more than 70% of COPD patients are currently categorized as having stage I to early stage II COPD, most of whom have no or very few respiratory symptoms (Zhong NS, et al. Am J Respir Crit Care Med. 2007, 176:753-760; Mapel DW, et al. Int J COPD 2011; 6: 573−581). The vast majority of these patients would have the “COPD assessment Test” (CAT) score of 10 or lower (range: 0 to 40, with higher scores indicating more severe COPD). Admittedly, no medication has been recommended for this patient cohort according to the latest international guidelines. In real-world practice, these patients are almost neglected by physicians and have received virtually no medication. Nonetheless, the annual lung function decline rates among these patients are the most rapid among all COPD patients. (Bhatt SP, et al. Am J Respir Crit Care Med 2015; 191: A2433). An important clinical question has been raised regarding whether an intervention strategy targeting at early stages of COPD can possibly make the airflow limitation more reversible or prevent from further deterioration.

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Studies Reinforce Efficacy of Ofev in Idiopathic Pulmonary Fibrosis

MedicalResearch.com Interview with:

Dr. Luca Richeldi MD PhD Professor of Respiratory Medicine Chair of Interstitial Lung Disease University of Southampton United Kingdom

Dr. Luca Richeldi

Dr. Luca Richeldi MD PhD
Professor of Respiratory Medicine
Chair of Interstitial Lung Disease
University of Southampton
United Kingdom

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The data presented at CHEST 2016 were from two post-hoc pooled analyses of the Phase III INPULSIS® trials that evaluated Ofev in idiopathic pulmonary fibrosis, or IPF. Both analyses, using different measures, demonstrate Ofev efficacy in a range of people with IPF, regardless of disease severity at the start of the trials.

One analyses investigated the efficacy of Ofev on disease progression in subgroups of patients defined by their GAP (gender, age, physiology) stage. Based on the index, patients were categorized as either GAP stage I or II/III. The analysis showed a similar reduction in disease progression with Ofev versus placebo regardless of GAP stage – meaning no significant difference between GAP stage I versus GAP stage II/III. Disease progression was defined as an absolute decline in forced vital capacity (FVC) ≥5% predicted or death over 52 weeks.

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Acute Respiratory Distress Syndrome Often Underrecognized, Has High Mortality

MedicalResearch.com Interview with:

John G. Laffey MD Chief, Department of Anesthesia; Co-Director, Critical illness and Injury Research Centre; Scientist, Keenan Research Centre for Biomedical Science ‑ St. Michael's Hospital Professor, Anesthesia, Critical Care, and Physiology ‑ University of Toronto

Dr. John Laffey

John G. Laffey MD
Chief, Department of Anesthesia; Co-Director, Critical illness and Injury Research Centre; Scientist, Keenan Research Centre for Biomedical Science ‑ St. Michael’s Hospital
Professor, Anesthesia, Critical Care, and Physiology ‑ University of Toronto

Medical Research: What is the background for this study?

Dr. Laffey: Acute respiratory distress syndrome is the commonest cause of severe acute respiratory failure in the critically ill. ARDS is a major cause of death and disability in the critically ill worldwide. Second, there is no treatment for ARDS, and our present management approaches are limited to supporting organ function while treating the underlying causes

We performed the LUNG SAFE study to address several clinically important questions regarding ARDS.

First, the current incidence in a large international cohort was not known. Large regional differences had been suggested: for example, the incidence of ARDS in the US was reported to be ten times greater of that in Europe_ENREF_4.

Second, we wanted to understand how we manage patients with  Acute respiratory distress syndrome in the ‘real world’ situation. Specifically, it was not clear to what extent newer approaches to artificial ventilation, such as reducing the size of the breaths (lower tidal volumes) and keeping the lung pressure positive at all times to minimize collapse (PEEP) were used. The impact of studies showing promise for other measures to improve gas exchange such as turning patients prone during mechanical ventilation, or using neuromuscular blockade, on routine clinical practice in the broader international context was not known.

Third, there were some concerns over the extent of clinician recognition of ARDS. This was an important issue because implementation of the effective therapies may be limited by lack of recognition of ARDS by clinicians. A better understanding the factors associated with ARDS recognition and how this recognition influenced patient management could lead to effective interventions to improve care.

Lastly we wanted to determine the outcome from  Acute respiratory distress syndrome in a global cohort of patients.

Medical Research: What are the main findings?

Dr. Laffey: We found that ARDS continues to represent an important public health problem globally, with 10% of ICU patients meeting clinical criteria for ARDS. While there appeared to be some geographic variation, this did not seem as great as previously thought.

An important finding was the under-recognition of  Acute respiratory distress syndrome by clinicians, with 40% of all cases not being recognized.

In addition, over one third of patients did not receive protective lung ventilation strategies. The use of other measures to aid gas exchange during artificial ventilation, such as turning the patient into the prone position, or the use of neuromuscular blockade was also quite low.

Of most concern, ARDS continues to have a very high mortality of approximately 40% of patients dying in hospital.

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Denim Sandblasters At High Risk of Pulmonary Silicosis

MedicalResearch.com Interview with:
Metin Akgun, MD, FCCP

Department of Pulmonary Medicine
Atatürk University, Faculty of Medicine
Erzurum, Turkey

Medical Research: What is the background for this study? What are the main findings?

Dr. Akgun: The first cases of silicosis due to denim sandblasting were reported in 2005. In 2007, we evaluated 145 former male denim sandblasters who had an exposure history to at least 1 month with a latency period at least ten months; 77 (53%) were diagnosed as silicosis according to the profusion category of opacities of 1/0 or greater. In this study, we reported 4-year follow-up results of this cohort. Out of 83 sandblasters who were evaluated in this follow-up study, nine died and of the remaining 74, 96% had radiographic evidence of silicosis based on the same criteria and 66% had pulmonary function loss, which was defined as at least 12% or more decrease on FVC, predicted.

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