 Introducing Elliot Israel, MD, and Juan Carlos Cardet, MD, MPH


 The strategy and findings of the PREPARE trial


 How to initiate patient-activated reliever-triggered inhaled corticosteroid


 The effect of COVID-19 on real-world asthma trials


 How to lessen the disparities of asthma


in late April showed Black and Latinx adults with 

 benefitted from the addition of a patient-directed, quick-reliever provisional inhaled glucocorticoid therapy along with their usual care.

The findings contribute to the prospect of implementing simpler care strategies for patients with difficult-to-control asthma, as well as feasible steps toward reducing asthma outcome disparities among people of color.

This May, during Asthma Awareness Month, the concept of PREPARE trial and its leading investigators headline a comprehensive discussion around mitigating key challenges in the chronic respiratory disease.

The newest episode of Lungcast features PREPARE investigators Elliot Israel, MD, of Harvard Medical School and Brigham and Women’s Hospital, and Juan Carlos Cardet, MD, MPH, of the University of South Florida Morsani College of Medicine.

Along with host Albert Rizzo, MD, chief medical officer of the American Lung Association (ALA), the research team discussed guideline-supported SMART strategy, the role of COVID in current asthma risks, and their own research into the disparate medical and financial impacts of asthma on the US patient population.

Lungcast is a monthly respiratory health podcast series from the ALA produced by 

Subscribe or listen to Lungcast on your favorite platforms:

https://open.spotify.com/show/1F3u1hKrwxi9snSQ0q3nti

https://podcasts.apple.com/us/podcast/lungcast/id1524712350

Podcasts

Elliot Israel, MD, and Juan Carlos Cardet, MD, MPH, join Lungcast to discuss their latest research into addressing Black and Latinx asthma outcome disparities.

How PREPARE Data, SMART Recommendations Alter Modern Asthma Strategy

A new investigation found that family history was an important contributor to the pathogenesis of obstructive sleep apnea (OSA), and was responsible for much of its effect on mediated by loop gain and neck size.

the American Thoracic Society 2020 International Conference

Previous research found that first-degree family history of OSA could be a potential risk factor for the sleep disorder, with estimates stating indicating ~40% of the variation in the apnea-hypopnea index (AHI).

However, the mechanisms of this effect have not been fully established.

As such, an investigative team led by Jeremy Orr, MD, Pulmonary and Critical Care Medicine at UC San Diego, tested the hypothesis regarding the effect of family history on AHI and how it is mediated through 1 or more known traits underlying OSA pathogenesis.

Orr and colleagues created a retrospective cohort based on a previous chart review of consecutive patients who were diagnosed with OSA (AHA≥5) based on an in-lab polysomnogram between January 2017 and December 2018. Each patients family history-status was explicitly noted.

The investigative team quantified 4 pathophysiological traits for each subject, including anatomical collapsibility, arousal threshold, loop gain, and pharyngeal dilator recruitment, which were determined via a validated polysomnography-based algorithm.

Following log-transforming of the AHI to increase normality, Orr and colleagues performed simple mediation analyses that included structural equation models. From there, the 4 traits and 2 proxy-markers of anatomical collapsibility functioned as candidate mediators, with age and sex being included as covariates.

A total of 355 patients with OSA were included in the study, all of whom had available data on family history of OSA and OSA traits. Among these patients, 104 (29%) has positive family history of OSA.

Investigators noted that both groups were similar in term of BMI, race and ethnicity. However, patients with a positive history of OSA tended to be younger compared to those without a positive history, with the median ages being 50 and 56, respectively.

Patients with a positive family history also tended to be female (50% versus 41%), and had more severe OSA based on a higher AHI (29 [17-60] vs 23 [12-50]).

Additionally, a positive family history was associated with a 37% (eβ=1.37) (P=0.001) higher AHI, partially mediated by loop gain (P>0.4). As such, this did not mediate its effect on the AHI.

In addition to confirming family history as an “important contributor” of OSA, the investigative team also believed this study suggested that high loop gain be considered as an endotype/phenotype for genome-wide association studies that focus on the genetic underpinnings of OSA.

“However, the majority of family history’s effect on AHI was not explained by traditional traits and markers of an unfavorable anatomy, and residual confounding or reverse causation cannot be excluded,” the team wrote.

Articles

Patients with a positive family history of OSA  tended to be female with more severe OSA based on a higher AHI.

Family History of OSA Contributes to Pathogenesis of the Condition

A recent investigation into obstructive sleep apnea (OSA) in pediatric patients with pulmonary hypertension (PH) found that a majority of patients were affected by the sleep disorder, prompting investigators to suggest routine screening for OSA in this population.

The new data was presented this weekend at 

 in San Francisco during the session, “Risk for Obstructive Sleep Apnea in Pediatric Patients with Pulmonary Hypertension”.

Obstructive sleep apnea has previously been associated with pulmonary hypertension in literature, with investigators citing a “complex and bidirectional relationship” between the 2 conditions. 

Though previous research has indicated a relationship between OSA and PH, little is known of the risk factors for the sleep disorder in younger populations. A better understanding of these risk factored could result in earlier and more meaningful treatment.

As such, and investigative team led by Daniel Ignatiuk, MD, of the Cincinnati Children’s Hospital, conducted an analysis of OSA risk factors documented in a 10-year cohort of pediatric patients with PH at the Cincinnati Children’s Hospital.

The team conducted a retrospective chart of patients 0-21 years with a documented diagnosis of PH who underwent diagnostic polysomnogram (PSG) between January 2010 and August 2020.

The first polysomnogram was analyzed in patients with multiple studies.

Exclusion criteria were PSG with sleep time less than four hours, tracheostomy tube, positive pressure ventilation, oxygen titration with less than 2 hours of diagnostic sleep time, and PSG more than 90 days before PH diagnosis or more than 90 days after PH resolution.

Meanwhile, PH was classified according to 6th World Symposium on PH criteria.

Only 2 patients with PH were excluded due to small group size.

Incidence of sleep disorders and OSA risk factors based on documented diagnoses and PH classification were the outcome variables.

A total of 403 patients were identified, with the final cohort including 89 patients with a median age of 3.6 years.

Classification of PH included group 1 (n=25, 28.1%), group 3 (n=31, 34.8%), and group 1/3 for patients meeting both group 1 and 3 criteria (n=33, 37.1%).

Diagnosed sleep disorders included OSA (n=79, 88.8%), central sleep apnea (n=11, 12.4%), hypoventilation (n=6, 6.7%), non-apneic hypoxemia (n=28, 31.5%), and periodic limb movement disorder (n=5, 5.6%).

Investigations observed that OSA risk was increased with a diagnosis of trisomy 21 (RR 1.24, 95% CI 1.09-1.42) (P<0.05).

Notably, OSA risk was decreased with group compared to group 1/3 PH (RR 0.84, 95% CI 0.71-0.99) (P<0.05) or group 3 PH (RR 0.81, 95% CI 0.68-0.96) (P<0.05), and no difference in OSA risk between group 1 and group 3 PH was seen.

Overall, OSA was diagnosed in a majority of pediatric patients in the study, most notably in patients with trisomy 21 or PS classification meeting both group 1 and 3 criteria.

“Our research supports routine screening for OSA in this population, and especially among patients with trisomy 21 or PH classification meeting both group 1 and 3 criteria,” the team wrote. “Further studies are needed to examine the impact of intervention on clinical outcomes.”

Significant OSA Prevalence in Pediatric Patients with Pulmonary Hypertension 

 indicated that an as-needed, fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide resulted in significantly lower risk of severe asthma exacerbation than abluterol alone in patients with uncontrolled moderate to severe asthma who were receiving a variety of inhaled glucocorticoid-containing maintenance therapies.

the American Thoracic Society 2022 International Conference

Traditionally, short-acting β2-agonist (SABA) rescue therapy will be utilized in patients whose asthma symptoms worsen. However, SABAs are not intended for addressing worsening inflammation.

Research has indicated that a fixed-dose combination of albuterol and budesonide would reduce the risk of severe asthma exacerbation when compared to albuterol alone.

Alberto Papi, MD, from the Department of Respiratory Medicine at the University of Ferrara Medical School in Italy, led a team of investigators in conducting a multinational, double-blind, phase 3 trial that evaluated the efficacy and safety of albuterol-budesonide as a rescue medication.

The investigative team enrolled adults and adolescents 12 years and older with uncontrolled moderate to severe asthma who were receiving inhaled glucocorticoid-containing maintenance therapies at the time. These therapies were continued during the trial.

Eligible patients were randomized 1:1:1 to 1 of 3 trial groups including a fixed-dose combination of albuterol at a dose of 180 μg and budesonide at a dose of 160 μg, a fixed-dose combination of albuterol at a dose of 180 μg and budesonide at a dose of 80 μg, or albuterol at a dose of 180 μg.

Notably, children 4 to 11 years were randomly assigned to either the lower-dose combination groups or the albuterol-only group. Among the 3132 patients included in thr trial, 97% were 12 years or older.

Papi and colleagues defined the primary endpoint as the first severe asthma exacerbation in a time-to-event analysis.

The team observed that severe asthma exacerbation was significantly lower in the higher-dose combination group, specifically by 26%, when compared to the albuterol-alone group (hazard ratio, 0.74, 95% confidence interval). (P=0.001).

Compared to the albuterol-only group, the hazard ratio in the lower-dose combination group was 0.84 (95% CI, 0.71 to 1.00) (P=0.052), and the incidence of adverse events were similar across all trial groups.

Research has indicated that a fixed-dose combination of albuterol and budesonide could better reduce the risk of severe asthma exacerbation when compared to albuterol alone.

Severe Asthma Exacerbation Risk Reduced with Combined Albuterol-Budesonide

New data suggests that the treatment of idiopathic pulmonary fibrosis (IPF) with BI 1015550- an oral preferential inhibitor of the phosphodiesterase 4 (PDE4) subtype- either alone or with an antifibrotic agent prevented a decrease in lung function.

The phase 2 data was published today in the New England Journal of Medicine to coincide with 

 taking place in San Francisco from May 13-18.

Currently, only 2 approved antifibrotic drugs- nintedanib and pirfenidone- are available to slow the progression of fibrosis in patients with IPF. This suggests that additional treatments could be used either with or instead of existing antifibrotic therapies.

Furthermore, PDE4 inhibition has been associated with positive anti-inflammatory and antifibrotic effects that researchers have deemed beneficial to patients with IPF.

An investigative team led by Luca Richeldi, MD, PhD, of the Catholic University of Sacred Heart, sought to determine the efficacy and safety of BI 1015550 in patients with IPF.

This multicenter, randomized, double-blind, phase 2 trial enrolled patients 40 years or older with a previous diagnosis of IPF, with patients with a usual interstitial pneumonia or a pattern of probable usual interstitial pneumonia on high-resolution computed tomography of the chest being deemed eligible for inclusion.

Patients with a forced vital capacity (FVC) were of at least 45% of the predicted value and a diffusing capacity of the lungs between 25% and less than 80% of the predicted value.

Those included in the study were permitted to continue the use of nintedanib or pirfenidone if they had been receiving a stable dose for at least 8 weeks leading up to screening.

The study utilized a total of 90 sites from 22 countries, of which eligible participants were selected and randomly assigned 2:1 to receive BI 1015550 at a dose of 18 mg twice daily or a matching oral placebo for 12 weeks.

Overall, 150 patients were deemed eligible for inclusion, with 147 undergoing randomization.At least 60 patients being randomly assigned to each group. The first patient underwent screening on August 12, 2020, and the last patient completed the trial on October 15, 2021.

The median change of FVC- the primary endpoint- among patients without background antifibrotic use was 5.7 ml (95% credible interval, –39.1 to 50.5) in the BI 1015550 group compared to –81.7 ml (95% credible interval, –133.5 to –44.8) in the placebo group.

Regarding patients with background antifibrotic use, median FVC was 2.7 ml (95% credible interval, –32.8 to 38.2) in the BI 1015550 group and –59.2 ml (95% credible interval, –111.8 to –17.9) in the placebo group.

Despite the relatively short nature of this trial, investigators felt it showed the stabilization of FVC with BI 1015550 therapy and provided a proof of concept for longer phase 3 trials. They added that a phase 3 trial would be necessary in evaluating these preliminary findings.

“The safety profile of BI 1015550, in combination with the observed effects on the FVC, warrants further research as a treatment for IPF and other forms of progressive pulmonary fibrosis,” the investigators wrote.

Patients treated twice-daily with an 18 mg dose of BI 1015550 experienced prevention of decreased lung function regardless of any background antifibrotic agents.

 BI 1015550 Effective in Prevention of Decreased Lung Function in IPF Patients 

The Sickle Cell Disease Association of America (SCDAA) was presented the Abbey S. Meyers Leadership Award by the National Organization for Rare Disorders (NORD). The annual award is given to organizations that warrant recognition for strong leadership in advocacy and education.

"It's been a tremendous honor for us to be recognized by NORD for the work that we've done," Regina Hartfield, President and CEO, SCDAA said in an interview. "I attribute this honor to all of those in the sickle cell disease community, who really deserve the praise--our warriors, our community based organizations, our partners, as with the fraternity, and also for the caregivers, and all of the clinicians that are involved in the care and the staff at the national office."

The funds that were granted to the association will support community programs, education, outreach, and awareness activities that the local community based organizations are involved in, Hartfield explained. 

SCDAA developed a clinical trial finder that is continually being improved upon and has expanded. Currently, the association is preparing to launch the clinical trial finder mobile app to provide more access for patients, providers, and caregivers who are interested in enrolling in a trial. 

"There are a lot of decision points that go into deciding whether or not someone wants to participate in a clinical trial," Harfield said. "And so, a lot of these conversations in families, having a mobile app will enable them to pull up information right then and there."

Videos

President and CEO of SCDAA Regina Hartfield discusses how the association will use the funds from the leadership award.

Regina Hartfield: NORD Recognizes SCDAA for Leadership

The long pursuit of a US Food and Drug Administration (FDA) approved treatment for non-alcoholic fatty liver disease (NAFLD).

Despite no currently approved therapies for the disease, there are currently more than 400 clinical trials involving NALFD in some compacity, at least 1 stakeholder is confident there will be an approved treatment in the next calendar year.

, Sanjiv Chopra, MD, Professor of Medicine, Harvard Medical School, said he hopes a treatment for NAFLD will finally be approved in as early as 6 months from now.

And while it can be difficult to predict how the US Food and Drug Administration might react, Chopra is confident they will approve a treatment for NAFLD.

“The FDA has gotten quicker and more efficient at approving drugs,” Chopra said. “I think we will see a bunch of these drugs approved in the next 6 months.”

Chopra said even with an FDA approval, care might not be transformed overnight.

“The challenge will be are the insurance companies going to pay for it and what is the cost going to be,” he said. For some of these drugs the cost is $1,200 or $1,500 a month. That’s a lot of money and many of the people who most need it will be the ones least likely to afford it.”

Dr. Chopra said an FDA-approved treatment for NAFLD could come in the next 6 months. 

Sanjiv Chopra, MD: Treatments for NAFLD on the Way

The US Food and Drug Administration (FDA) has approved tirzepatide (Mounjaro) injection, a novel, dual-targeted treatment to improve blood sugar control in adults with 

“Type 2 diabetes is a chronic and progressive condition that requires continued innovation to help people manage their blood glucose and weight," Mike Mason, president, Lilly Diabetes, said in a statement. "Today’s FDA approval underscores our commitment to the discovery and development of new treatment pathways, and we are thrilled to bring this new and innovative treatment option to people living with type 2 diabetes.”

The treatment, developed by Eli Lilly and Co., is to be used as an addition to diet and exercise, representing the first in-class treatment that activates both the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

Clinical trial results show the drug is effective at improving blood sugar more effectively than other diabetes therapies. A total of 3 doses (5 mg, 10 mg, and 15 mg) of the treatment were evaluated in a total of 5 clinical trials.

The drugs were tested as either a stand-alone therapy or as an add-on to other medications.

The 15 mg dose resulted in the lowering of hemoglobin A1c (HbA1c) level by 1.6% more than placebo when used as a stand-alone therapy and 1.5% more than placebo when used in combination with a long-acting insulin. This dose also resulted in the lowering of HbA1c by 0.5% more than semaglutide, 0.9% more than insulin degludec, and 1.0% more than insulin glargine.

Treatment with tirzepatide also resulted in an average weight loss of 15 pounds more than placebo when both were used with insulin, with an average weight loss with the 15 mg dose of 12 pounds more than semaglutide, 29 pounds more than insulin degludec and 27 pounds more than insulin glargine.

“Given the challenges many patients experience in achieving their target blood sugar goals, today’s approval of Mounjaro is an important advance in the treatment of type 2 diabetes,” said Patrick Archdeacon, MD, associate director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research, in a 

The approval represents the first in-class treatment that activates both GLP-1 and GIP.

FDA Approves Tirzepatide for Patients With Type 2 Diabetes

 was "New Drugs for the PCP: Outpatient Treatment of 

" led by Gerald Smetana, MD, Professor of Medicine, Harvard Medical School, Clinician Educator, Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center.

Smetana highlighted the key points of his presentation and went into a detailed discussion of the outpatient treatment options for the virus in an interview with 

. Every year at this conference, he talks about new drugs in primary care, but this year, Smetana decided to use his limited time on stage to focus on outpatient management of COVID-19.

"I really think it's the most important new drug advance for primary care clinicians," he said, "and in particular, I think, because many of us might be uncomfortable in that venue, and not confident in prescribing these medicines."

Smetana acknowledged that PCPs might be hesitant to prescribe monoclonals because they think these drugs are outside of their usual scope of practice, which is true, he said. However, the current position of primary care providers puts them in the role of prescribing outpatient treatments for the virus and he encouraged providers to get comfortable with monoclonal antibodies.

"We're on the front lines, we're the ones who are getting these phone calls," Smetana explained, "and we just simply don't have the time between when symptom onset occurs and patients have to be treated to get those types of subspecialty consultations."

With the emergence of various strains of COVID-19, the treatment landscape is ever-changing. And while he talks about the various monoclonal antibodies, right now, bebtelovimab is the only one that's retained an emergency use authorization (EUA) from the US Food and Drug Administration (FDA) for all variations of the virus.  

The Oral Antiviral Treatment for COVID-19

Nirmatrelvir-ritonavir (Paxlovid) is the first oral antiviral treatment of COVID-19 that's been deemed safe for the same indication as bebtelovimab--outpatients with the virus who are at risk of progression to severe disease. In addition to being safe, a primary advantage to this drug is that it's administered orally, rather than needing infusions like monoclonal antibodies. 

Smetana clarified that a few important things providers need to consider to when prescribing nirmatrelvir-ritonavir. It's crucial to be very thorough when checking for 

. Also, the adjusted dosage guidelines for patients with kidney disease must be followed. 

The treatment was approved in December and needs to be given to the patient within 5 days of symptom onset. Fortunately, nirmatrelvir-ritonavir has recently become available in commercial pharmacies and should be 

widely accessible now in most communities

"This is possible to get at local pharmacies, not just academic medical centers," he said. "It has to be given within 5 days of symptom onset, which is an important barrier. So, patients have to call us as soon as possible after testing positive. And because we do have that short window, this is why, you know, we're going to be the primary prescribers for that drug."

Dr. Gerald Smetana encourages PCPs to familiarize themselves with the outpatient drug options for managing COVID-19 because of the limited treatment window for administration.  

Gerald Smetana, MD: Outpatient COVID-19 Treatment Relies on Primary Care Providers

The US Food and Drug Administration (FDA) has approved drug-eluting stent (DES) Onyx Frontier, from Medtronic, for the treatment of patients with 

The new DES product leverages the same platform as Medtronic’s Resolute Onyx, designed to improve the delivery of drugs and improve acute performance.

The company cited a 16% improvement in deliverability observed with Onyx Frontier versus the previous generation DES Resolute Onyx. Additionally, the new stent provides a 2.0 mm diameter, adding to stent size spectrum that ranges up to 6.0 mm for treated patients. The FDA indication granted to Onyx Frontier is the same as granted to Resolute Onyx, meaning it may be provided in care to patients who also may be at high risk of bleeding when treated with a dual antiplatelet therapy (DAPT) regimen for ≥1 month.

As the leading cause of death for both men and women in the US, CAD may be effectively treated with minimally-invasive application of a stent. The newest DES approval will benefit interventional cardiologists treating more complex cases with greater efficiency given the vessel size flexibility of the Onyx Frontier, Azeem Latib, MD, section head of interventional cardiology and medical director of structural heart interventions at Montefiore Medical Center, said in a statement.

"Delivering safe and effective outcomes to our patients is our number 1 priority,” Latib said in a statement. “It's important that physicians have access to tools like the Onyx Frontier DES that can allow them to efficiently achieve those outcomes."

Medtronic senior vice president and president of the Coronary & Renal Denervation business at Medtronic Jason Weidman, called the DES approval a “very important milestone” in the company’s coronary care venture.

“The Onyx Frontier launch also correlates directly to Medtronic's commitment to engineering,” Weidman said. “The team built upon the design and clinical successes of the Resolute Onyx DES and has continued to evolve proven DES technology to further address the needs of physicians. We look forward to continuing the pursuit of innovation each day."

The new drug-eluding stent can provide more flexible width size for patients with the potentially deadly disease.

FDA Approves New Medtronic Stent for Coronary Artery Disease

news page, resources on the topics of disease- and specialty-specific medical news and expert insight can be found. Content includes articles, interviews, videos, podcasts, and breaking news on health care research, treatment, and drug development.

All News

Latest News