It’s been an exciting past decade or so in the field of respiratory health, and current research is making particular strides in the field of air quality-related health.

But for as much has been found to progress the clinical understanding of air pollution’s relationship with patient outcomes, there’s a lot more left to uncover, Sonali Bose, MD, told 

In a sit-down interview, Bose, an assistant professor at Icahn School of Medicine at Mount Sinai, reflected on some of the biggest topics discussed at the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, this year. In speaking ahead to what’s left to be uncovered by pollution health researchers, Bose pointed to individual exposure estimates as well as the factors that make a patient more susceptible or resilient to the effects of air quality.

It’s a crucial topic — not only does air pollution span a person’s lifetime, but it’s among the most threatening current public health issues, Bose said.

“In contrast to some of the other public health concerns we have, people often feel that they are vulnerable to these effects without much control over how much exposure they get,” Bose said.

Sonali Bose, MD: Checking in on Air Quality Health Research

America’s diversity can be well-defined by its pollution exposure rates. There are, indeed, socioeconomic or ethnic subpopulations that report greater vulnerability to air pollution effects.

As John R. Balmes, MD, from the University of California, San Francisco and Berkeley, noted in his presentation at the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, it’s the US economic system that perpetuates environmental inequality.

“And the people that are best able to protect themselves from air pollution — either by buying a clean motor vehicle or living in a nice, clean neighborhood &mdash; set the rules,” Balmes said. “They have the political power that keeps the folks that are poor and of color with greater environment exposures.”

It’s abundantly clear to other clinicians, such as Sonali Bose, MD, that pollution more greatly affects vulnerable populations in the US. The assistant professor at Icahn School of Medicine at Mount Sinai told 

it can be observed in hospital admissions, patient symptoms, and through the progression of diseases such as asthma and chronic obstructive pulmonary disease (COPD).

Though Bose lauded the “fantastic job” of US officials in reducing indoor cigarette exposure through public health strategy and federal indoor smoking regulations, she said there are still sources of indoor and outdoor air pollution that need to be addressed domestically — especially in urban environments.

“We end up seeing vulnerable populations who have a tremendous continued exposure, and these can lead to significant adverse effects,” Bose said.

Sonali Bose, MD: Indoor and Outdoor Air Pollution in the US

In the QUEST and VENTURE study results presented at the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, last week, researchers lauded metrics which showed dupilumab (Dupixent) significantly reduced independence from oral corticosteroids (OCS) in patients with uncontrolled asthma.

Indeed, a large conversation piece held at ATS pertained to therapy regimens that could relieve the burden of OCS from patients with asthma. This conversation more particularly applies to pediatric patients, Sonali Bose, MD, told 

Bose, an assistant professor at Icahn School of Medicine at Mount Sinai, said OCS has been linked to harmful growth-related adverse effects, and comorbid asthma conditions such as diabetes and heart disease. She called the ATS rhetoric a “fantastic” address of a chronically understood issue.

“Anything we can do to minimize the steroid burden on patients with diabetes is welcome,” Bose said.

Another focal point in progressive asthma care — not just at ATS, but in the field itself &mdash; is in the treatment of type 2 inflammation. Due to asthma being a heterogeneous disease, Bose said clinicians cannot afford to adopt a “one size fits all” approach to a condition that fluctuates in its response to immunotherapy.

Individual factors, such as age or race, and how they influence therapies are yet to be understood. Perhaps they will be the headline conversations of next year’s ATS meeting.

“I think we’ll see in the next few years a more personalized approach to try to understand which patients will have the most benefit with these targeted therapies,” Bose said.

Sonali Bose, MD: Reducing Corticosteroids and Type 2 Asthma Inflammation

The US Food and Drug Administration (FDA) approved once-daily inhaled corticosteroid (ICS) fluticasone furoate (Arnuity Ellipta) for the maintenance treatment of children from 5 years old with asthma last week, aligning the GlaxoSmithKline therapy with only a handful of once-daily therapies marketed for pediatric asthma patients. According to GSK, the field is still in dire need of more convenient treatment options, 

The therapy, from GlaxoSmithKline (GSK), now joins a small list of once-daily therapies licensed in the country for this particular pediatric asthma population — a space still in need of more convenient treatment options, according to GSK. Director and Project Physician Lead Dr. Sanjeev Khindri, in the days following the drug's announced approval during the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, reflected on the major clinical development and detailed what more is to come in the field of pediatric asthma.

MD Magazine: Can you provide some more background into the details of the trials supporting fluticasone furoate for children with asthma? What were chosen as important metrics to gauge, speaking particularly to pediatric patients?

Dr. Sanjeev Khindri: The submission included data from a pivotal study [HZA106855] assessing the efficacy and safety of once daily fluticasone furoate in children aged 5-11 years (inclusive) with uncontrolled asthma (symptomatic on either SABA alone, SABA plus non-ICS controller or SABA plus low-dose ICS). In the pivotal study [HZA106855] 593 children were randomized (1:1:1:1:1) to receive either placebo once daily, fluticasone propionate 100 mcg twice daily, or fluticasone furoate 25 mcg, 50 mcg, or 100mcg once daily. Note that this study also evaluated dose response for 3 strengths of ARNUITY and included fluticasone propionate as an active comparator. The primary endpoint of the 12-week study was the mean change from baseline in daily morning peak expiratory flow (PEF). Two further studies assessed the effects of inhaled once-daily fluticasone furoate in children aged 5-11 years (inclusive): one study [HZA107112] looked at effects on lower leg growth (assessed via knemometry) and another study [HZA107118] evaluated its effect on the hypothalamic-pituitary-adrenocortical axis (assessed using serum cortisol). The approved dose in children aged 5-11 years in the US is 50 mcg once-daily, delivered using the Ellipta inhaler.

There is reference made to the difficulties of running clinical studies with the age group Arnuity Ellipta is now indicated for. Can you elaborate on the challenges of pediatric asthma trials, and how GSK research responded to such challenges to achieve supporting clinical results?

The challenges in this age group (5-12 years old) are multi-faceted and linked. Complexity of recruiting and retaining children in clinical studies wherein scheduling has to take account of not only the child but the parent/caregiver, anxiety and significant stress around blood tests and conducting spirometry in children and compliance with treatment and assessments. Feedback from parents, children and investigative staff was instrumental in refining study design and procedures in the completing the two subsequent safety studies and in the currently ongoing Phase III study (HZA107116: NCT03248128) of FF combined (fixed dose) with vilanterol (VI) in children with persistent asthma (see below). The important changes/strategies we adopted were: use of animated, targeted consent/assent for children, provision of dedicated study rucksacks for children, establishing buddies such that participating would not be the only patients at clinic visits, discussions and agreements to remove/limit safety blood tests/ECGs given prior data for both FF specifically and the ICS class more widely and familiarization visits to site including spirometry.

Is there any plan to conduct longer-duration, or extension trials for Arnuity Ellipta?

We are currently undertaking a 12-month, placebo-controlled study (HZA114971: NCT 02889809) to evaluate and quantify the effect of FF 50 mcg on growth velocity as measured by stadiometry in pre-pubertal children in asthma. This study is part of Pediatric Study Plan agreed with the US FDA. The study is due to complete in 2022. Whilst we are not planning any further/extension studies for Arnuity Ellipta in asthmatic children aged 5-12, we have recently started a global phase 3, 6-month study (HZA107116: NCT03248128) to evaluate the safety and efficacy of FF/VI  in children aged 5-18. In those aged 5-12 we will be evaluating FF/VI 50/25 versus FF 50 whilst in those aged 12-18 we will be evaluating FF/VI 100/25 versus FF 100. This latter study is part of an agreed Pediatric Study Plan for FF/VI (Breo) in the US and Paediatric Investigation Plan in the EU.          

The treatment is now among only a few for this patient population. How important is it for the addition of new, more effective and more tolerable therapies for children with asthma?

It is critically important we provide prescribers and their patients/parents with a choice of effective and safe medicines that have been evaluated in appropriate and robust clinical trials. The approval of Arnuity Ellipta 50 mcg for children aged 5-12 based on the clinical study package discussed above provides a safe and effective medicine delivered in an easy to use once-daily device.

Q&A: Fluticasone Furoate Reaches Pediatric Asthma Market

US Food and Drug Administration’s (FDA) approval of fluticasone furoate

 (Arnuity Ellipta) was for pediatric patients with asthma, it was as welcome to physicians tasked with managing asthma in children.

Sonali Bose, MD, an assistant professor at Icahn School of Medicine at Mount Sinai, told 

the indication gives physicians just another option to reduce oral corticosteroid use while preserving pediatric lung function in children.

“This is also great news because it also gives us the confidence to prescribe this medication in children for maintenance,” Bose said.

The current burdens of pediatric asthma treatment are only amplified by the difficulty of testing a once-daily therapy in a clinical trial setting with children patients, Bose noted. Even then, physicians are tasked with addressing a wide array of modern issues in each new patient: environmental factors have worsened over years, as has the pediatric obesity rate.

That said, she finds it particularly exciting to be in the field at a time when clinicians are embracing a comprehensive approach to care.

“I think, for the first time, we’re getting an expansive understanding of all the other factors that are playing a role in asthma, and trying to target them in a global fashion,” Bose said.

From gestational studies to researching respiratory preservation through adolescence, the current pediatric asthma field is honed in on bettering the individual patient.

“If we can find a simple way of delivering medications once a day in a way that will help to reduce the burden of symptoms and other effects, then I think we’re on the right track,” Bose said.

Sonali Bose, MD: Fluticasone Furoate and Other Therapies for Pediatric Asthma

At the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, Paratek Pharmaceuticals presented a new analysis of the phase 3 Omadacycline for Pneumonia Treatment in the Community (OPTIC) study of omadacycline (OMC), a first-in-class aminomethylcycline, demonstrating non-inferiority to moxifloxacin (MOX), a fluoroquinolone, for treatment of adults with community-acquired bacterial pneumonia (CABP).

Regardless of severity of disease, data showed similar high rates of response for early clinical response (ECR) and post therapy evaluation (PTE) endpoints in both the OMC and MOX treatment groups.

“This analysis underscores that across the range of severity measured, reaching ECR occurs in a high percentage of hospitalized CABP patients,” Paul McGovern, MD, vice president, clinical and medical affairs, Paratek, told 

“This is important because in clinical practice, reaching ECR is likely to result in transition from IV to oral omadacycline allowing for early hospital discharge. That in combination with the PTE results, is a positive gauge that with omadacycline treatment, CABP patients will be able to go home and stay home, which is exactly the kind of simple solution treating physicians are looking for.”

OPTIC, a randomized (1:1) double-blind, global study compared the safety and efficacy of daily, IV-to-oral OMC to IV-to-oral MOX for a duration of 7—14 days in 774 adults (intent to treat population, n = 386 OMC, n = 388 MOX) with radiologically confirmed CABP. After a minimum of 3 days of intravenous treatment, subjects could transition to oral treatment if clinical stability criteria were met.

ECR (72—120 hours after first dose) was defined as survival, no receipt of rescue antibacterial therapy and improvement in at least 2 of the 4 CABP symptoms (cough, sputum production, pleuritic chest pain, dyspnea) without deterioration in any of the symptoms. The US Food and Drug Administration (FDA) considers ECR as a primary outcome in patients with CABP.

Other outcome measures included PTCR (5—10 days after last antibiotic dose), which defined as survival and resolution or improvement of signs and symptoms to the extent that further antibacterial therapy was not necessary.

The primary objective of OPTIC was to evaluate ECR by Pneumonia Research Outcomes Team (PORT) Risk Class, while the secondary objective was to evaluate post therapy clinical response (PTCR).

Additionally, the safety and tolerability, assessed by treatment-emergent adverse effects, vital sign measurements, ECGs and laboratory values were also measured.

Patients had a PORT Risk Class of II (14.2% OMC, 13.9% MOX), III (58.8% OMC, 55.7% MOX) or IV (26.4% OMC, 29.6% MOX).

Data showed that OMC was associated with fewer treatment-emergent side effects than MOX (10.2% vs. 17.8%, respectively).

A high percentage of patients in both treatment arms (75% to 80%) reached the FDA endpoint of ECR in each PORT Risk Class.

Additional analyses in subgroups with higher mortality risk of higher severity are consistent with the PORT Risk Class clinical success at ECR and PTE.

“While fluoroquinolones are among the most commonly prescribed antibiotics, the class presents issues due to mounting evidence of safety concerns and 

 infections,” McGovern added. “There is a growing body of evidence to support limiting the use of fluoroquinolones within the context of antimicrobial stewardship programs.”

OMC has been granted Qualified Infectious Disease Product designation and Fast Track by the FDA, and the new drug applications for CABP and acute bacterial skin and structure infections (ABSSSI) have been accepted for priority review with an expected decision in October 2018.

“If approved, OMC may offer an effective monotherapy alternative to fluoroquinolones, with similar, high rates of ECR and PTE, regardless of the severity of disease,” McGovern concluded.

Omadacycline Demonstrates Non-Inferiority to Moxifloxacin in Treatment of CABP

The amount of patients with asthma or chronic obstructive pulmonary disease (COPD) who can properly use their inhaler is a debated number. But regardless of its true rate, the number is too low.

One presentation at the 2017 Annual CHEST Meeting

 last year provided metrics from a recent European study which suggested less than 40% of observed patients were unable to perform a perfect inhalation, regardless of the provided device.

At the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA this year, 

 which showed patients significantly struggled to manage proper inhaler use when using multiple devices versus a lone device — the triple-therapy Trelegy Ellipta, which is only inhaler therapy of its kind in the US.

In all the current asthma-related issues driven by pediatric obesity, pollution rates, and limited convenient therapy options, that patients being able to adhere to and properly take inhaler therapy is among the issues is almost shocking. But it’s a common conversation in the doctor’s office, Sonali Bose, MD, said.

The assistant professor at the Icahn School of Medicine, Mount Sinai, told 

that inhaler adherence and proper use is certainly a significant issue. In fact, its prevalence was so severe that physicians were initially looking for other explanations.

“A lot of what we thought about previously as being severe asthma actually ends up being asthma that is difficult to treat because of these issues in the way patients have been taking their medications — not only in terms of their inhaler technique, but also in terms of their adherence,” Bose said.

Bose advocates for partnerships with nurses and pharmacists to emphasize proper practice at the end of patient visits, and for physicians to also take it upon themselves to dissect the issue during their own check-ups. There’s a promising endgame for improved inhaler adherence and use.

“Our hope is that improved adherence and improved technique in their inhaler medications will lead to downstream affects in asthma control,” Bose said.

The Importance of Proper Inhaler Use

As comorbidities and associations linking other conditions to asthma continue to be explored in clinical settings, facilities and practices are better off treating patients with a team-based approach across multiple disciplinaries. Such an approach has been embraced by the Mount Sinai Health System in New York. Sonali Bose, MD, an assistant professor at the system's Icahn School of Medicine detailed to MD Magazine how Mount Sinai has collaborated and initiated new means of addressing respiratory health issues.

MD Magazine: What practices have been adopted at Mount Sinai to improve patient respiratory health care?

Sonali Bose, MD: We're happy to announce that Mount Sinai has partnered up with National Jewish Health from Colorado to establish an independent health facility called the Mount Sinai National Jewish Respiratory Institute. And by doing that, we've hoped to allow for more specialty care in respiratory disease. One of the efforts that's been made has been allowing more resources to be available for patients particularly with asthma.

I'm one of a few asthma providers there and one of the things that I've found to be very beneficial has been the partnerships within our institution, specifically with ear, nose, and throat specialists and allergists to allow for a multidisciplinary approach in the way that we care for our asthma patients. We've been able to incorporate various technologies and different equipment, in order to better assess what's been going on in both the upper and lower airways to help us provide a more targeted approach to some of the things that might be making their asthma worse.

We're also very grateful to have access to some of the environmental components that are important in asthma management, and teaming up with pharmacists and nurses has been very useful for patients to feel like they can reach out and address their concerns about their drugs and how they're using them as well. So I think the newly established respiratory institute has been a very nice platform to allow patients to have a more comprehensive degree of asthma care.

What research has been undertaken by Mount Sinai to advance clinical understanding in the field of respiratory health?

Mount Sinai has speared a number of research initiatives recently to advance our clinical understanding of how to approach asthma, and this has spanned the life course. We are very active in research to look at prenatal exposures and environmental exposures very early in life that can predispose children to developing asthma and other respiratory outcomes. This has been a huge initiative over the last few years.

We have also an active field of research that has partnered up with different drug companies to see how different therapeutics might be useful in managing patients that we see. And this has spanned across the board — not just asthma, but a lot of other respiratory diseases. We're fortunate to have put together a team that has been quite cross-disciplinary from the other fields to try to get a more diverse understanding of this. We have researchers in the microbiome, we have exposure scientists, we have a number of implementation scientists as well, that have all worked together to understand in a more global way, what are the things we can do to improve asthma.

Sonali Bose, MD: Respiratory Care and Research at Mount Sinai

At the 2018 American Thoracic Society (ATS) International Conference in San Diego, California, Prometic Life Sciences presented new clinical data assessing PBI-4050 on blood biomarkers for treatment of idiopathic pulmonary fibrosis (IPF), concluding that PBI-4050 alone or in combination with nintedanib demonstrated promising efficacy.

The recent analysis revealed that PBI-4050, the lead candidate in a pivotal phase 2/3 clinical trial, significantly increased levels of biomarkers known for antifibrotic effects, suggesting the potential as an antifibrotic, anti-inflammatory and pro-tissue repair mechanism.

“The drug turned out to be very safe, and I think it will offer a nice combination,” Joe Parker, MD, senior director, 

“If it proves effective in the larger trial, it’ll be a nice alternative either as monotherapy or in combination with nintedanib to be more effective than current therapy, and maybe with less side effects.”

The main objective of the exploratory study was to determine whether treatment with PBI-4050 alters the level of key biomarkers in 41 enrolled patients. Subjects with a confirmed diagnosis of IPF received daily oral doses of 800 mg PBI-4050 with (n = 9) or without nintedanib (n = 16) or pirfenidone (n = 16) for 12 weeks. Baseline characteristics were similar to those in previous randomized controlled studies.

After 2 weeks, 1 subject on PBI-4050 and pirfenidone withdrew because of an unrelated treatment-emergent adverse effect of IPF exacerbation and is not included in the analysis.

Biomarkers chosen for measurement were divided into 2 main groups: cytokines and matrix metalloproteinases associated with fibrosis and inflammation.

Researchers concluded that PBI-4050 was safe and well tolerated as a monotherapy or in combination with nintedanib and pirfenidone.

The mean change from baseline to week 12 in forced vital capacity (FVC) on PBI-4050 both alone or in combination with nintedanib was stable, -12 mL and +2 mL, respectively, while it decreased significantly by -104.7 mL for PBI-4050 in combination with pirfenidone because of a drug-to-drug interaction.

Researchers observed a significant increase (greater than 10%) for IL-9, IL-7 and MIP-1β, reflecting a change in the balance between a profibrotic and an inflammatory, wound-healing environment.

“This [PBI-4050] would provide an alternative option for patients who are actually intolerant of 1 of the 2 current drugs,” Parker added. “It also would allow for patients on nintedanib, if they are still progressing on their drug, to have another option to improve their rate of declines and they would be better in that regard."

Patients who responded to PBI-4050 treatment were recorded as having significantly higher serum plasminogen levels indicating the importance of plasminogen in IPF.

Daily oral treatment with 800 mg PBI-4050 with or without nintedanib or pirfenidone for 12 weeks demonstrated a strong safety profile in those with IPF. There no deaths, no patients experiencing a decline of 10% of their FVC and no treatment-emergent adverse effects required study drug discontinuation.

The most common treatment adverse effect was diarrhea in all groups, however, it was less significant in patients receiving PBI-4050 alone.

PBI-4050 alone and in combination with nintedanib indicated promising efficacy when compared to those receiving PBI-4050 in combination with pirfenidone.

The effects of the small molecule candidate demonstrated in animal models have been replicated in phase 2 studies in IPF, metabolic syndrome with type 2 diabetes and Alström syndrome, and is currently involved in pivotal placebo-controlled phase 3 clinical trials for treatment of IPF.

PBI-4050 Demonstrates Promising Efficacy Results for IPF Treatment

Corey Bradshaw, PhD, opens his presentation with a graphic designed by climate scientist Ed Hawkins: the steady rise of monthly global temperature changes, depicted as a 12-angle circle that reaches outward more and more, year over year.

The final image, a spiraling rainbow sphere with an ominous “2017” pasted at the core, tells its own story: this is as bad as it’s ever been, and it can get worse.

In his presentation at the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, Bradshaw, an author and professor at Flinders University, Adelaide, South Australia, said the current average temperatures being reported now haven’t been prevalent in about 2.5 million years.

The threats of pollution’s effects on global health — 

from particulate matter and ozone concentration

 possibly triggering more respiratory hospitalizations, to pediatric asthma rates spiking in areas of greater pollution — have been well-documented over the years. But Bradshaw drew on the characteristics of worsening pollution and global warming rates to explain how the planet is on an accelerating pace to devastation.

The human population rate is “not going anywhere fast,” Bradshaw noted. He explained how accumulating the deaths counted in both World Wars, a fictional 5-year third World War, the Spanish flu pandemic of 1918, an amalgamation of other public health crises, and a global nuclear exchange would still leave estimates for a population of approximately 5 billion people at the end of the century.

In no place population resiliency more prevalent than in Africa, Bradshaw said. The continent will have 5.5-7 times as many residents than its current population size over the next century, growing from 500 million to nearly 3 billion. The rate is the highest of any continent in the world by at least twice the next-greatest increase.

“The fertility decline seen in other places of the world have not been manifested in Africa,” Bradshaw said. “In some countries, they are stable or even increasing.”

Bradshaw explained that population density has become a good predictor of environmental damage — studies have shown that countries that protect more land have a greater environmental footprint.

Greater population density results in greater use of natural resources — natural forest loss, habitat conversion, marine captures, fertilizer use, water pollution, carbon emissions &mdash; and threat to the land’s biodiversity.

The results of a recent ranking of countries with the worst environmental damage came as no surprise to Bradshaw, as some of the most densely-population countries ranked near the top (Brazil, United States, China ranked 1-3, respectively). But the other distinguishable factor was country wealth.

Bradshaw explained the theory of the Environmental Kuznets curve — a hypothesis from economist Simon Kuznets that really has no role in environmental metrics as it does modern capitalism.

“The theory is that, as you increase capital prosperity and develop a nation, your environmental damage increases as you begin to exploit more of your resources — followed by some sort of middle class achieving education standards and access to cleaner technologies,” Bradshaw said.

As a result, environmental damage would be reduced by increases in national wealth. But, as indicated in 

another ATS session focused on wealth and environmental disparity in the US

“We found that wealth is the only driver that predicted most variation of countries with environmental damage,” Bradshaw said. “If anything, there was an increasing linear effect of increasing wealth and environmental damage.”

Bradshaw likened the burdens of population growth, wealth disparity, and resource abuse to having a bank account with $1000 in it. If a person earned $20 annually and spent $30 annually, they can survive on the reserve fund’s account for a while before running dry.

“This is the concept of the ecological footprint, which is essentially the amount of environment necessary to support a particular lifestyle,” Bradshaw said.

On average, the human population is “spending” the resources of about 1.6 Earths per year. On its current pace, humanity would overshoot global resource budgets by June 29, 2030. If carbon emissions were reduced by 30%, the overshoot date would be delayed — by only 79 days.

“A lot of people say there’s no evidence the environment is affecting our capacity,” Bradshaw said. “Well, that’s because we’re running down on reserves.”

How Population and Global Resources Are Reaching a Boiling Point

Diet, in the treatment of many conditions, can make or break the patient's response to care. Though the correlation between asthma prevalence or progression and food intake is well-documented, researchers are still trying to draw definite conclusions from the association. Such findings were heavily discussed at the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, this year, where Sonali Bose, MD, joined in the rhetoric.

, Bose talked the present knowledge of diet and ashtma, and what's hoped for in the future.

What is the significance of diet in asthma maintenance and prevention?

Sonali Bose, MD: The role of diet in asthma prevention and treatment has been a very hot topic in the last 5-10 years, and has made a lot of press this year at ATS, mainly because we've had a number of studies that have shown relationships between individual dietary patterns and their asthma control, or their propensity to develop asthma later in life.

A few of those highlights have been looking at people's intake of omega fatty acids, vitamin D, as well as more global assessments of diets, such as the Mediterranean diet. You'll be hearing a lot of press about those.

It's still not clear what the relationships are. Some of the findings that were presented relate to the individual relationship of what you're eating and its consequence on asthma control. And it may not be so simple as that. Additional data was presented that looked at the relationship of diet as a susceptibility factor to other insoles like air pollution. In other words: does diet make you more resilient to the effects of air pollution, or more susceptible? 

And some of these results are very promising in a way that can really empower individuals to say, "Okay, I'm faced with bad air pollution in my environment, but what can I do about it? And can I maintain a healthy diet to help buffer against the adverse effects of that exposure?" And I'm hoping that we'll see a lot more in the future, particularly with intervention trials, to see if that can make a difference with people's health.

Sonali Bose, MD: Diet's Role in Asthma Care

New data, presented at the 2018 American Thoracic Society (ATS) International Conference in San Diego, California, suggests that combining home oxygen therapy (HOT) with home non-invasive ventilation (HMV) as treatment for chronically hypercapnic chronic obstructive pulmonary disease (COPD) is more effective and cost-efficient than HOT alone.

Researchers compared the accumulated costs of devices, doctor visits, medications and hospitalizations to HOT alone using a US economic model, and concluded that HOT-HMV saved on average per year, $3927 per patient.

“If you can keep people out of the hospital that’s usually going to be cost-effective. In the US, admissions to the hospital are very expensive, they are less expensive in the UK, which is why the study indicated even greater cost-effectiveness in the US than it did in the UK,” David White, MD, chief scientific officer, Philips Respironics, professor of medicine, Harvard Medical School, told 

“In the US, the holy grail with COPD these days is keeping them out of the hospital, particularly these people that are exacerbating frequently, because a hospitalization in that setting costs $20,000 plus, and if you can avoid 1 hospitalization, that’ll cover way over the cost of the equipment.”

The data, obtained by an economic analysis of a Philips-sponsored clinical trial of 116 patients in the UK, suggests that the combination of non-invasive ventilation (NIV) and HOT can significantly prolong time to readmission or death for patients with COPD following a life-threatening respiratory event or exacerbation. The 5-year study resulted in prolonged median time to readmission or death by nearly 3 months and improved patient health-related quality of life in the first 6 weeks.

The original data were used to develop an economic model from a US payer perspective, which was presented at this year’s ATS meeting. The analysis indicated the base-case incremental cost per quality-adjusted life year (QALY) gained was negative $50,856, recommending HOV-HMV both in order to save costs and improve quality of life compared to HOT alone.

The economic analysis enrolled patients with a hospital admission due to an exacerbation of COPD requiring active NIV with chronic hypercapnia 2—4 weeks following resolution of respiratory acidosis.

Those patients enrolled in the control arm were permitted to have HMV added to HOT if the primary endpoint, hospital readmission, was met, and if preset safety criteria were breached like persistent acidosis and inability to wean from NIV.

The analysis included patient-level evaluation of equipment, patient-reported medication, physician office visits and hospital admissions because of exacerbations.

Costs were calculated by multiplying observed medical resource utilization by standard unit costs and summed at the patient level.  

Analysis results included information from 28/59 HOT patients and 36/57 HOT-HMV patients that completed the 12-month study, with 17 patients allocated to HOT receiving additional HMV.

Researchers concluded that within 30 days, hospital readmission was 58.3% lower in the intervention group. The total costs were $24,458 for HOT-HMV and $28,386 for HOT alone. Patients on HOT-HMV, costs were $4,298 for devices, $10,805 for doctor visits, $758 for medication, and $8,598 for exacerbations; while costs for HOT alone were $1,582, $15,033, $1,088, and $10,683, respectively.

Per the bootstrap analysis, the probability indicated for HOT-HMV to both save costs and improve quality of life is 75.7%.

A similar analysis conducted in the UK also indicated cost-effectiveness and demonstrated greater device costs, a savings of £2,328 per patient in doctor visits, medication and hospitalization costs.

Asked about how these data will better help clinicians treat patients managing COPD, White recommends putting patients that are chronically hypercapnic on NIV to not only reduce costs for the health care system but improve patient’s lives.

Philips Respironics is currently working on a novel way to manage NIV in this patient population. The device, which will be coming out in the next 6—12 months, aims to make it more comfortable and easier for COPD patients to utilize NIV.

HOT-HMV Treatments for COPD Could Reduce Annual Cost of Care

Chronic obstructive pulmonary disease (COPD) patients oftentimes have frequent exacerbations that require emergency departments visits and hospitalizations, which is associated with increased health care utilization, especially when those patients have low adherence to long-acting bronchodilators. Clinical studies suggest that electronic inhaler monitoring (EIM), which consists of tools that allow real-time tracking of medication utilization, fosters adherence and ultimately reduces health care utilization.

Cleveland Clinic researchers initiated an EIM program for patients with COPD and high health care utilization and reported the results at the 2018 American Thoracic Society (ATS) International Conference, in San Diego, California. 

, Umur Hatipoglu, MD, Cleveland Clinic, discussed why electronic inhaler monitoring is associated with lower healthcare utilization among COPD patients with frequent hospitalization and ED visits. 

How is adherence of electronic inhaler monitoring for patients with COPD associated with lower health care utilization?

Umur Hatipoglu, MD:  We prescribe medications, inhaled medications for patients with COPD all the time. It's really the cornerstone of their therapy, and when they return to the clinic we do ask them whether they're using their medications or not and we are left with yes or no. Yes I'm using it, no I'm not using it.

But the reality is, there's a continuum of use. People are adherent a percentage of the time to their medications, and we never know what that number is objectively. I think electronic inhaler monitoring allows that to happen. You basically have the patient with you, and you'd have a percentage of adherence. And if that percentage of adherence is lower than what is expected, you could conduct a discussion with the patient as to why that may be. Maybe they're not even aware, it's unwitting adherence problems and this could potentially improve patient outcomes.

So this was basically the gist of the idea, in incorporating electronic inhaler monitoring to the care of patients with COPD.

ATS 2018 Perspectives

EP 1: Sonali Bose, MD: Checking in on Air Quality Health Research

EP 2: Sonali Bose, MD: Indoor and Outdoor Air Pollution in the US

EP 3: Sonali Bose, MD: Reducing Corticosteroids and Type 2 Asthma Inflammation

EP 4: Q&A: Fluticasone Furoate Reaches Pediatric Asthma Market

EP 5: Sonali Bose, MD: Fluticasone Furoate and Other Therapies for Pediatric Asthma

EP 6: Omadacycline Demonstrates Non-Inferiority to Moxifloxacin in Treatment of CABP

EP 7: The Importance of Proper Inhaler Use

EP 8: Sonali Bose, MD: Respiratory Care and Research at Mount Sinai

EP 9: PBI-4050 Demonstrates Promising Efficacy Results for IPF Treatment

EP 10: How Population and Global Resources Are Reaching a Boiling Point

EP 11: Sonali Bose, MD: Diet's Role in Asthma Care

EP 12: HOT-HMV Treatments for COPD Could Reduce Annual Cost of Care

EP 13: Umur Hatipoglu, MD: Electronic Inhaler Monitoring in COPD Patients