Inhaled Steroids Associated With Increased Risk of Atypical Mycobacterial Infections

MedicalResearch.com Interview with:

Stephen J Ruoss MD Professor, Stanford University, Medicine, Division of Pulmonary and Cfritical Care Medicine Stanford, California

Dr. Ruoss

Stephen J Ruoss MD
Professor, Stanford University, Medicine,
Division of Pulmonary and Cfritical Care Medicine
Stanford, California

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by an atypical mycobacterial infection? 

Response: Our interest in undertaking this study stems from three important clinical observations and issues.

First, the use of inhaled steroid medications for a broad variety of respiratory complaints and diseases is increasing, including in clinical circumstances where there isn’t much strong supportive evidence for benefit to patients from using inhaled steroids.

The second observation is that steroids can and do alter immune system responses, and can increase the risk for some infections. There are already data from studying patients on inhaled steroids where the incidence of bacterial respiratory infections has increased, supporting the concerns for infection risk from inhaled steroids.

And the third issue is that steroids can more specifically alter immune system function that helps combat mycobacterial infections, and this means that the risk for, and incidence of mycobacterial infections could be increased in patients treated with inhaled steroids. The best known mycobacterial infection is of course tuberculosis, but there are other mycobacteria, called nontuberculous mycobacterial (or atypical mycobacterial) that are broadly found in the environment, and some of those nontuberculous mycobacteria (NTM) can cause lung infections.

So our hypothesis was that the use of inhaled steroids might be associated with an increased frequency of NTM infections, and we designed the study to explore that hypothesis. Continue reading

Some Pulmonary Embolism Patients Can Be Treated at Home

MedicalResearch.com Interview with:

Joseph Bledsoe MD, FACEP Clinical Assistant Professor of Emergency Medicine Stanford Medicine Director of Research Department of Emergency Medicine Intermountain Medical Center Murray, UT 84157

Dr. Bledsoe

Joseph Bledsoe MD, FACEP
Clinical Assistant Professor of Emergency Medicine
Stanford Medicine
Director of Research
Department of Emergency Medicine
Intermountain Medical Center
Murray, UT 84157

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

Response: Patients with blood clots in the lungs (pulmonary embolism) (PE) are routinely admitted to the hospital for blood thinning medications in the United States. However, evidence from other countries has shown that with appropriate risk stratification patients may be safe for outpatient treatment for their PE.

Our study is the largest prospective management study in the US to evaluate home treatment of patients with acute pulmonary embolism. We enrolled 200 patients and after risk stratification with the PE severity index score, leg ultrasounds and echocardiograms performed in the emergency department, patients were treated with blood thinning medications at home with routine outpatient follow up.

During the 90 day follow up period we found only one patient suffered a bleeding event after a traumatic injury, without any cases of recurrent symptomatic blood clots or death.  Continue reading

Daily Chest X-Rays Still Overused in Mechanically Ventilated Patients

MedicalResearch.com Interview with:

Hayley B. Gershengorn, MD Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida Division of Critical Care Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York

Dr. Gershengorn

Hayley B. Gershengorn, MD
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida
Division of Critical Care Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York

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

Response: Beginning in December, 2011, professional guidelines have recommended against the practice of daily chest radiography (CXRs) for mechanically ventilated patients.  However, we hypothesized that this practice was still commonplace in the US and varied from hospital to hospital.

To address this question, we performed a retrospective cohort study of >500,000 mechanically ventilated adults across 416 US hospitals. We found that 63% of these patients received daily CXRs and that, while use has been decreasing, this decrease is small (a 3% relative reduction in the odds of daily CXR receipt per discharge quarter starting in 2012).

Moreover, the hospital at which a patient received care greatly impacted the likelihood of daily CXR receipt.

Continue reading

COPD: Vaporized Cannabis Did Not Reduce Breathlessness or Improve Exercise Capacity

MedicalResearch.com Interview with:

“Cannabis sativa” by Manuel is licensed under CC BY 2.0

cannabis

Sara Abdallah, PhD Student, first author and
Dennis Jensen, PhD Associate Professor,
Department of Kinesiology and Physical Education
Associate Dean – Infrastructure, Faculty of Education
Director, McGill Research Center for Physical Activity and Health
Canada Research Chair in Clinical Exercise & Respiratory Physiology
Associate Member, Translational Research in Respiratory Diseases Program
Research Institute of the McGill University Health Center

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

Response: Many patients with chronic obstructive pulmonary disease (COPD) suffer from severe breathlessness at rest and on minimal exertion despite receiving optimal drug therapy for their underlying disease (e.g., bronchodilators). In these patients, breathlessness significantly diminishes exercise capacity and quality of life. Thus, research focused on identifying adjunct therapies for management of breathlessness in patients with advanced COPD is clinically relevant.

A series of studies conducted in the 1970’s found that smoked cannabis caused bronchodilation (i.e., improved airway function) in healthy individuals and in patients with asthma. More recently, it has been demonstrated that delta-9 (∆9)-tetrahydrocannabinol (THC, the major cannabinoid constituent of cannabis) inhibits cholinergic contractions in isolated human bronchi and that a positive association exists between measure of lung function (e.g., forced expiratory volume in 1-sec) and cannabis use in patients with COPD. These studies lead us to hypothesize that inhalation of vaporized cannabis may alleviate exertional breathlessness and improve exercise tolerance in patients with advanced COPD by improving airway function at rest and during exercise. Continue reading

Specific Microbial Signatures Differentiate Chronic Coughs in Children

MedicalResearch.com Interview with:

Dr. Mikhail Kazachkov MD Director of Pediatric Pulmonology Hassenfeld Children’s Hospital NYU Langone Medical Center

Dr. Kazachkov

Dr. Mikhail Kazachkov MD
Director of Pediatric Pulmonology
Hassenfeld Children’s Hospital
NYU Langone Medical Center 

MedicalResearch.com: What is the background for this study? How common is the problem of chronic cough in children?  Is it more common in children with allergies, asthma or reflux?

Response: Chronic cough is one of the leading causes of pediatric referrals to subspecialty physicians.  Its prevalence in the general pediatric population may approach 3% (Galassi et al, Epidemiol. Prev. 2005;29,Suppl.:9–13).

It is important to recognize that the main causes of chronic cough in children are completely different for those in adults.  Specifically, gastroesophageal reflux and postnasal drip are not considered to be important causes of cough in children.  Cough variant asthma, although is a common cause of cough in adults, does not seem to be frequently diagnosed and a cause of chronic cough in children.

The main cause of chronic wet cough in children is protracted bacterial bronchitis (Chang et al, Chest. 2017 Apr;151:884-890).  It is important to recognize that neurologically impaired children have completely different pathogenesis of chronic cough, which is mostly related to aspiration into the lower airway and development of aspiration-related lung disease.

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SUNSET Trial Supports Bronchodilators as Foundation of COPD Therapy

MedicalResearch.com Interview with:

Kenneth R. Chapman, MD MSc FRCPC FACP FCCP, FERS Director, Asthma & Airway Centre, University Health Network, Professor of Medicine, University of Toronto, GSK-CIHR Research Chair in Respiratory Health Care Delivery, Toronto, Ontario

Dr. Chapman

Kenneth R. Chapman, MD MSc FRCPC FACP
FCCP, FERS
Director, Asthma & Airway Centre, University Health Network,
Professor of Medicine, University of Toronto,
GSK-CIHR Research Chair in Respiratory Health Care Delivery,
Toronto, Ontario

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

Response: Guidelines regard inhaled bronchodilators as foundational pharmacotherapy in COPD while inhaled corticosteroids are to be used sparingly.  Inhaled corticosteroids are used to reduce exacerbation tendency but come with the added risk of pneumonia, osteoporosis and other corticosteroid related adverse effects.  Although only a minority of COPD patients are exacerbation prone, many patients with COPD are treated unnecessarily with inhaled corticosteroids alongside long-acting anticholinergic and beta2 agonist bronchodilators – so-called “triple therapy”.  In patients who have minimal exacerbation histories, inhaled corticosteroid withdrawal is suggested to reduce side-effects.

Although studies have suggested this is a reasonable strategy, study limitations have been noted.  The best known inhaled corticosteroid withdrawal study, the WISDOM trial, recruited only 39% of patients using triple therapy regularly before inhaled corticosteroid withdrawal; the remainder were placed on triple therapy solely for the purposes of the withdrawal study.

In the SUNSET trial, long term triple therapy patients with no more than one exacerbation in the preceding year were randomized to continue triple therapy or to de-escalate to a second generation dual bronchodilator therapy – indacaterol/glycopyrronium 110/50 once daily.  This one step de-escalation better mirrored clinical practice than the gradual tapering approach of the WISDOM trial.  There was no increase in exacerbations after de-escalation and although average FEV1 decreased by 26 ml in the group that de-escalated, the decrease is so small as to be immeasureable in individuals.  In a post-hoc analysis, a subset of patients with persistently elevated blood eosinophil counts (greater than 300 cells per uL) were the ones most likely to have exacerbations in follow-up or to have changes in FEV1.  Continue reading

Early Study Demonstrates Airways Can Be Transplanted from Aortic Templates

MedicalResearch.com Interview with:
Emmanuel Martinod MD PhD
Assistance Publique–Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Chirurgie Thoracique et Vasculaire, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny,
Université Paris Descartes, Fondation Alain Carpentier, Laboratoire de Recherche Bio-chirurgicale, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou
Paris, France 

MedicalResearch.com: What is the background for this exciting new technology and study? What are the main findings? 

Response: What is the background for this exciting new technology and study? What are the main findings?

Response:  The background is 10 years of research at laboratory followed by 10 years of academic clinical research.

We demonstrated the feasability of airway bioengeenring using stented aortic matrices for complex tracheal or bronchial reconstruction.  Continue reading

Pneumonia Patients on Ventilators May Benefit from New Ceftolozane/Tazobactam Antibiotics

MedicalResearch.com Interview with:

Dr. Elizabeth Rhee MD Director, Infectious Disease Clinical Research at Merck

Dr. Rhee

Dr. Elizabeth Rhee MD
Director, Infectious Disease Clinical Research Merck

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

Response: High-risk patients, such as the critically ill, with suspected bacterial infections require prompt treatment with appropriate empiric therapy to improve survival. Given the high prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa in the ICU setting, new safe and broadly effective treatment options are needed for critically ill patients requiring antipseudomonal agents.

Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin/beta-lactamase inhibitor combination with broad in vitro activity against Gram-negative pathogens, including MDR P. aeruginosa and many extended-spectrum beta-lactamase (ESBL) producers. It is FDA approved for complicated intra-abdominal and urinary tract infections in adults at 1.5g (1g/0.5g) q8h. C/T is currently being studied at 3g (2g/1g) q8h, for the treatment of ventilated nosocomial pneumonia, in the ASPECT-NP Phase 3 trial.

This Phase 1 pharmacokinetic (PK) study investigated the penetration of a 3g dose of C/T in the epithelial lining fluid (ELF) of ventilated patients with proven or suspected pneumonia. This is the dose and patient population being evaluated in ASPECT-NP. ELF lines the alveoli, and investigators took samples in a group of 26 patients to see what amount of C/T was in the lung and what was circulating in the plasma during the dosing intervals.

In mechanically ventilated critically ill patients, the 3g dose of C/T achieved ≥50% lung penetration (relative to free plasma) and sustained levels in ELF above the target concentrations for the entire dosing interval. These findings support the 3g dose that is included in the ASPECT-NP Phase 3 trial.  Continue reading

X-Linked Genetic Signatures Linked To Respiratory Disorders in Males

MedicalResearch.com Interview with:

Gustavo Nino, M.D. Children’s National Health System pulmonologist Study senior author

Dr. Nino Barrera

Gustavo Nino, M.D.
Children’s National Health System pulmonologist
Study senior autho

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

Response: The epidemiology of respiratory disorders is largely influenced by the individual’s sex resulting in overall higher risk for males than females, particularly during early life. Hormonal, anatomical and behavioral differences are postulated to play a role, but these sex-based respiratory differences are already present at birth, suggesting a strong genetic component. However, the genetic differences in the airways of males and females during early life have been remarkably understudied and are largely unknown.

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