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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IPF Patients Treated With Nintedanib (Ofev) More Likely To Have Stable Lung Function

MedicalResearch.com Interview with:

Kevin R. Flaherty

Dr. Flaherty

Kevin R. Flaherty, M.D., M.S.
Professor, Department of Internal Medicine
Associate Director, T32 Multidisciplinary Training Program in Lung Diseases
Chair, Pulmonary Fibrosis Foundation Clinical Care Network Steering Committee
University of Michigan Medicine 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This is a new post-hoc analysis, recently presented at the 2017 American Thoracic Society (ATS) conference, which sought to further assess the efficacy of Ofev (nintedanib), an FDA-approved drug treatment for idiopathic pulmonary fibrosis (IPF), and its effect on lung function in those with this disease.

IPF is a rare and serious lung disease that causes permanent scarring of the lungs and affects as many as 132,000 Americans.

The analysis examined pooled data from the two placebo-controlled, global Phase III INPULSIS trials, which evaluated the efficacy and safety of 52 weeks’ treatment with nintedanib in people with IPF. In both trials, a higher proportion of people treated with placebo than nintedanib had disease progression from baseline to week 52, as defined by the proportions of patients with ≥5% or ≥10% declines in lung function, as measured by forced vital capacity (FVC) % predicted. Additionally, a lower proportion of patients treated with placebo than nintedanib had no decline or an improvement in FVC % predicted.

These data support the initial findings from the Phase III INPULSIS trials which found that more patients treated with nintedanib versus placebo had an absolute decline in FVC of less than 5%.

In this subgroup analysis, we assessed the proportions of patients from the two INPULSIS trials treated with nintedanib and placebo who had no decline or an improvement in lung function from baseline to week 52 using pooled data for this post-hoc analysis. In terms of those who participated, a total of 864 patients were included (519 treated with nintedanib, 345 treated with placebo). Baseline characteristics including age, gender and FVC were similar between the subgroups of patients who had no decline or an improvement in FVC and those whose FVC declined, and between the nintedanib and placebo groups within each subgroup.

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Vascular Biomarker Predicts Death or Pulmonary Morbidity in Premature Infants

MedicalResearch.com Interview with:

Jegen Kandasamy MD Division of Neonatology Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program University of Alabama at Birmingham Birmingham, Alabama

Dr. Kandasamy

Jegen Kandasamy MD
Division of Neonatology
Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program
University of Alabama at Birmingham
Birmingham, Alabama 

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

Response: Preterm infants, especially those that are born with a birth weight of 750 grams or less, are prone to a lung disease called bronchopulmonary dysplasia (BPD) because the development of lungs in these infants takes place in an environment that has more oxygen than that available in utero. Recently, pulmonary blood vessel growth and function has been hypothesized to play a causal role in the pathogenesis of BPD. Vascular endothelial cell function has been shown to affect hyperoxia-induced lung damage in animal studies. An important source of human vascular endothelial cells is the umbilical cord of newborn infants. These human umbilical venous endothelial cells (HUVEC) have been used to measure endothelial cell function in various diseases but never in diseases related to the newborn infants from whom they were derived.

In addition, the mitochondria in various cells in our body respond to oxygen toxicity by creating, as well as consuming, reactive oxygen species (ROS) that mediate most of the effects of oxygen-induced damage. Therefore, we designed this study to measure mitochondrial function in vascular endothelial cells obtained from the umbilical cords of prematurely born infants at the time of their birth. We then compared these mitochondrial functional measures between infants who later died or developed BPD versus those who survived without BPD.

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T Cell Biomarkers Predictive of Course of IPF – Idiopathic Pulmonary Fibrosis

MedicalResearch.com Interview with:

Catherine Bonham MD Section of Pulmonary and Critical Care Medicine University of Chicago

Dr. Bonham

Catherine Bonham MD
Section of Pulmonary and Critical Care Medicine
University of Chicago

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

Response: Idiopathic pulmonary fibrosis (IPF) causes fibrosis, or scar tissue, to form in the lungs. People with IPF become more and more short of breath and need oxygen. It is progressive and we don’t have any cure. Prognosis is about 3 to 5 years, worse than many cancers. We don’t know what causes it. It is a leading indication for lung transplant.

Many doctors and scientists are skeptical about the role of the immune system in IPF because some immune-directed treatments, like steroids, have been tried and failed. However, recent research shows that the expression of genes in patients who do well with IPF is different from patients who do poorly and die rapidly from IPF. The difference in survival was in genes expressed by their immune systems, specifically their T cells. We have known for decades that T cells are a type of white blood cell specialized for fighting infection. In the last several years, doctors and scientists made the amazing discovery that T cells also fight cancer within the body. Many new immune therapies have now been developed that can make some patients cancer-free. It was very exciting to think that T cells could also affect survival in pulmonary fibrosis.

My study followed 59 patients with Idiopathic pulmonary fibrosis for up to 5 years, and examined whether we could measure two molecules on the surface of CD4 T cells, and use them to predict survival for patients with IPF. These molecules are called ICOS and CD28. They function to activate the T cells, which creates a chain reaction activating other parts of the immune system.

A second part of my study looked at the lungs and lymph nodes from 9 IPF patients who generously donated their old lungs to research after they received lung transplant. The purpose of this was to find if what I see in blood samples reflected what the T cells really do in the lungs.

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First Patients Enrolled in Study of Nintedanib For Progressive Fibrosing Lung Conditions

MedicalResearch.com Interview with:

Thomas Leonard, Ph.D. Executive director, Clinical Development and Medical Affairs, Specialty Care Boehringer Ingelheim Pharmaceuticals, Inc.

Dr. Thomas Leonard

Thomas Leonard, Ph.D.
Executive director, Clinical Development and Medical Affairs, Specialty Care
Boehringer Ingelheim Pharmaceuticals, Inc.

MedicalResearch.com: What is the background for this study? Would you tell us a little more about IPF?

Response: Boehringer Ingelheim’s Phase III PF-ILD (progressive fibrosing interstitial lung disease) trial will investigate the safety and efficacy of nintedanib, in a range of progressive fibrosing lung conditions other than idiopathic pulmonary fibrosis, or IPF. The PF-ILD trial is the first time that patients with different fibrosing lung diseases will be included in one single clinical trial assessing the efficacy of nintedanib as a potential treatment, and the trial is the first in the field of fibrosing lung diseases to group patients based on the clinical characteristics of their disease, rather than the diagnosis.

There are more than 200 conditions that affect the tissue and space around the air sacs of the lungs, or interstitium, and, collectively, these conditions are called interstitial lung diseases — or ILDs. Based on clinical observations, there is a group of patients with ILD who, independent from the classification of the ILD, exhibit progressive fibrosis. The proposed terminology for describing this group of patients is PF-ILD. In these patients, the disease appears to follow a course similar to IPF with worsening of respiratory symptoms, lung function, quality of life and ability to perform daily activities, as well as early mortality despite treatment.

There is currently no efficacious treatment available for PF-ILD. This trial is exploring how fibrosis in the lungs is treated and whether nintedanib is a potential treatment, based on the efficacy and safety of nintedanib in IPF, a rare and serious lung disease that causes permanent scarring of the lungs, making it difficult to breathe. IPF affects as many as 132,000 Americans, typically men over the age of 65. On average, people with IPF live only three to five years after diagnosis, and approximately 40,000 people die from this disease every year.

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Bernie Williams Discusses His Dad’s Journey With IPF and New Treatment Options

MedicalResearch.com Interview with:

Mr. Bernie Williams Four-time World Series champion and star centerfielder for the New York Yankees discusses his beloved dad Bernabé’s struggle with a rare lung disease called idiopathic pulmonary fibrosis (IPF)

Mr. Bernie Williams

Mr. Bernie Williams

Four-time World Series champion and star centerfielder for the New York Yankees discusses his beloved dad Bernabé’s struggle with a rare lung disease called idiopathic pulmonary fibrosis (IPF) 


MedicalResearch.com: Would you briefly explain what idiopathic pulmonary fibrosis is? How does it affect a person’s health and ability to breathe?

Mr. Williams: IPF is a rare and serious lung disease that causes permanent scarring of the lungs, and makes it difficult to breathe. Symptoms of IPF include breathlessness during activity, a dry and persistent cough, chest discomfort, fatigue and weakness. Although considered “rare,” IPF affects up to 132,000 Americans, and about 50,000 people in the U.S. are diagnosed every year with IPF – enough to fill a baseball stadium.

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Which Patients With Advanced Respiratory Disease Die in the Hospital?

MedicalResearch.com Interview with:

Dr Sabrina Bajwah MBChB MRCGP MSc MA PhD Consultant Palliative Medicine, King’s College NHS Foundation Trust Honorary Senior Lecturer King's College London Cicely Saunders Institute, Department of Palliative Care, Policy and Rehabilitation London, UK

Dr Sabrina Bajwah

Dr Sabrina Bajwah
MBChB MRCGP MSc MA PhD
Consultant Palliative Medicine, King’s College NHS Foundation Trust
Honorary Senior Lecturer
King’s College London
Cicely Saunders Institute, Department of Palliative Care, Policy and Rehabilitation
London, UK 

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

Response: Where people die is often important to them and their families, as well as being important for planning health care services. Most people want to die at home, but instead most die in hospital. While the trends have been studied in cancer, other diseases, such as respiratory, are rarely looked at even though they are common and increasing causes of death.

Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Pulmonary Diseases (IPD) are common respiratory conditions. Both conditions result in a high use of hospital services, especially among people in advanced stages. This leads to high healthcare costs.1 In the UK in 2010, it is estimated that IPD costs £16.2 million per year in hospitalisations.2 The NHS spends more than £810 million annually managing COPD, with inpatient stays accounting for around £250 million annually.

Understanding which factors affect place of death is vital for planning services and improving care, especially given our ageing population, rising chronic diseases and the high costs of hospital admissions. Strategies in many countries have sought to improve palliative care and reduce hospital deaths for non-cancer patients, but their effects are not evaluated.

We aimed to determine the trends and factors associated with dying in hospital in COPD and IPD, and the impact of a national end of life care (EoLC) strategy3 to reduce deaths in hospital. This study analysed a national data set of all deaths for COPD and IPD, covering 380,232 people over 14 years.

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Cystic Fibrosis Patients Survive Ten Years Longer in Canada than in US

MedicalResearch.com Interview with:
Dr. Anne L. Stephenson, MD, PhD

St. Michael’s Hospital
Toronto Canada

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

Response: Both Canada and the US have maintained national registries on individuals with cystic fibrosis (CF) dating back to the 1970s. Previous reports suggested that survival differed between the two countries however direct comparisons of survival estimates between national registry reports were limited because of differences in methodologies used, data processing techniques and possible differences in the patients captured within each registry.

We aimed to compare survival in  cystic fibrosis between Canada and the US to determine if differences existed when we applied a systematic and standardized approach.

Our analysis showed that between 1990 and 2013, survival for individuals with CF increased in both countries, however, the rate of increase was faster in Canada compared to the USA. The survival gap widened at two distinct time points: 1995 and 2005.

In the contemporary period between 2009 and 2013, the median age of survival for individuals with cystic fibrosis in Canada was found to be 50.9 years compared to 40.6 years in the US. Overall, the risk of death was 34% lower for Canadians compared Americans with CF after adjusting for markers of disease severity. When US CF subjects were classified by insurance status, we found a 77% lower risk of death among Canadians with CF compared to Americans who indicated unknown or no insurance, a 44% lower risk compared to Americans receiving continuous Medicare/Medicaid, and a 36% lower risk in Canadians compared to Americans receiving intermittent Medicare/Medicaid. The risk of death for Americans with private insurance was not statistically different from that of Canadians with cystic fibrosis .

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Effects of Riociguat in Treatment-Naïve vs Pretreated Patients With Pulmonary Arterial Hypertension

MedicalResearch.com Interview with:

Prof. Hossein-Ardeschir Ghofrani University of Giessen and Marburg Lung Center Giessen, Germany, and Member of the German Center of Lung Research and Department of Medicine Imperial College London London, UK

Prof. Ghofrani

Prof. Hossein-Ardeschir Ghofrani
University of Giessen and Marburg Lung Center
Giessen, Germany, and
Member of the German Center of Lung Research
and Department of Medicine
Imperial College London
London, UK

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

Response: Pulmonary arterial hypertension (PAH) is characterised by increased pulmonary vascular resistance (increased resistance to blood flow in the pulmonary circulation), which can lead to right heart failure and death. Riociguat is the first of a new class of drugs – the soluble guanylate cyclase stimulators. It has been approved for the treatment of PAH based on the impressive efficacy and safety results from two pivotal Phase III studies: PATENT-1 and its long-term extension phase, PATENT-2. PATENT-1 was a 12-week, double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of riociguat in patients with PAH. Patients who completed PATENT-1 without ongoing riociguat-related serious adverse events (AEs) could enter PATENT-2, in which they received open-label riociguat. PATENT-1 admitted patients whether they were treatment-naïve or already receiving targeted PAH therapies, such as endothelin receptor antagonists (ERAs) and prostanoids. This current analysis compared the safety and efficacy of riociguat between treatment-naïve and pretreated patients in the PATENT-2 long-term extension study.

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Nanoparticles From Pollution Can Awaken Dormant Herpes Viruses in Lungs

MedicalResearch.com Interview with:

Dr. Tobias Stöger Group Leader, Dynamics of Pulmonary Inflammation Comprehensive Pneumology Center Institute of Lung Biology and Disease (iLBD) Helmholtz Zentrum München

Dr. Tobias Stöger

Dr. Tobias Stöger
Group Leader, Dynamics of Pulmonary Inflammation
Comprehensive Pneumology Center
Institute of Lung Biology and Disease (iLBD)
Helmholtz Zentrum München 

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

Response: Particulate air pollution is common in urban areas and the inhalation of nanoparticles is known to trigger inflammatory effects in humans potentially altering the immune system.

Herpes viruses are ubiquitous and well adapted pathogens hiding in host cells and persist thus continuing in a greater part of our population.

Under certain stress conditions and if the immune system becomes weakened, the viruses can become active again, begin to proliferate and destroy the host cell.

Thus we raised the question whether NP-exposure of persistently herpesvirus-infected cells as a second hit might provoke reactivation of latent virus and eventually lead to an inflammatory response and tissue damage.

Our main finding is that NP-exposure of persistently herpesvirus-infected cells – murine or human – restores molecular signatures found in acute virus infection and boosts production of lytic viral proteins.

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