The Decade in Review: 10 Years of Advancements and Moderation

By: Chidinma Chima-Melton, MD, FCCP

December 13, 2019

The Biggest Changes in Pulmonary, Critical Care, and Sleep Medicine Since 2010

As we close out this year and reflect back on advancements in the field of pulmonary and critical care medicine, we look back at a decade of breakthroughs. In the next #CHESTChat, we hope you will join us to discuss these breakthroughs!

The area with the most significant breakthroughs in our field is arguably pharmaceuticals. In 2012, the Food and Drug Administration (FDA) approved ivacaftor, the first drug to address an underlying cause of cystic fibrosis. Fast forward 7 years, we can now offer 90% of our patients suffering from cystic fibrosis life-changing, molecularly targeted therapies in the form of the recently FDA-approved elexacaftor–tezacaftor–ivacaftor combination [1].

The landscape of lung cancer care also shifted dramatically with immunotherapies extending the lives of our advanced stage lung cancer patients. Immune checkpoint inhibitors starting with the anti PD-1 (nivolumab and pembrolizumab) and later anti-PD-L1 (atezolizumab, durvalumab, avelumab) have changed the paradigm for non-small cell lung cancer treatment—and the future is looking bright [2].

Furthermore, we now have a class of the novel oral anticoagulants, including apixaban, dabigatran, rivaroxaban, and edoxaban, which provide safe and convenient oral alternatives to warfarin, allowing us to anticoagulate our VTE patients without the need for ongoing monitoring blood tests.

We also have two FDA-approved drugs, pirfenidone and nintedanib, that slow down lung function decline in patients with the devastating illness idiopathic pulmonary fibrosis for the first time, offering them hope but not a cure yet [3,4].

High Impact: Reviewing the Field’s Literature and Scientific Advances Since 2010

Although the importance of those breakthroughs cannot be overstated, the last decade was not just one of pharmacological advancements.

New practice techniques helped reduce morbidity and increase survival in critically ill patients. Some were inspired by the landmark 2013 study by Guerin that showed prone positioning reduced ARDS mortality by 26% [5]. Others were inspired by this year’s cutting-edge Lascarrou study indicating that targeted temperature management, done by cooling to 33°C, would lead to a favorable neurologic outcome in cardiac arrest victims [6]. It truly has been a brave new world in our field.

Despite these advancements, this was also a decade of moderation where we learned that sometimes less is more. For example, while red blood cell transfusions are often unavoidable, too much can be harmful, with studies showing more harm in cardiac patients transfused using a liberal strategy [7], and no benefit is associated with transfusion for hemoglobin above 7 g/dL in septic shock [8].

To further support this cautious approach, we also saw that overly intensive glucose control in critically ill adults leads to moderate and severe hypoglycemia, which increased the risk of death [9].

After early goal-directed therapy described by Rivers and colleagues in 2001 [10], it seemed that protocolized care in sepsis would be the rule. However, once again moderation won out with three large 2010s studies, ARISE (Australasia), ProCESS (United States), and ProMISe (United Kingdom) trial, clearly showing that usual care was noninferior with protocolized sepsis management [11-13].

Looking Ahead to the Next 10 Years

As we speculate about the upcoming decade, it is exciting to think about the role precision medicine will play in our field. Abandoning the one-size-fits-all mentality, pharmacogenomic biomarker drug labeling will allow us to better tailor medications to patients with specific biomarkers [14]. We will fully realize the promise of big data and artificial intelligence to better characterize and translate heterogenous disease states, such as IPF—and just as we have done with cystic fibrosis, we will offer these patients a hope for a cure.

On Thursday, December 19, at 8 pm CT, we’ll say goodbye to the 2010s and try to predict the future in an end-of-the-year #CHESTChat on Twitter. We hope you’ll join us!

T1: What were the biggest changes in the practice of pulmonary, critical care, and sleep medicine in the past decade?

T2: What were the highest impact articles/scientific advances in the field of pulmonary, critical care, sleep medicine in the past decade?

T3: What are the innovations/changes that you would like to see in the field of pulmonary, critical care, sleep medicine in the next decade?

T4: Finish this sentence "In 10 years. . ."

References

1. Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single phe508del allele. N Engl J Med. 2019;381(19):1809-1819.
2. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123-135.
3. Noble PW, Albera C, Bradford WZ, et al. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Eur Respir J. 2016;47(1):243-253.
4. Richeldi L, duBois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071-2082.
5. Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159-2168.
6. Lascarrou JB, Merdji H, Le Gouge A, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med. 2019 October 2. [Epub ahead of print].
7. Chatterjee S, Wetterslev J, Sharma A, et al. Association of blood transfusion with increased mortality in myocardial infarction: a meta-analysis and diversity-adjusted study sequential analysis. JAMA Intern Med. 2013;173(2):132-139.
8. Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371(15):1381-1391.
9. Investigators N SS, Finfer S, Liu B, et al. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012. 367(12):1108-1118.
10. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377.
11. Investigators A, Nguyen B, Havstad S, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371(16):1496-1506.
12. Pro CI, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683-1693.
13. Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-1311.
14. FDA. Table of pharmacogenomics biomarkers in drug labeling. www.fda.gov/downloads/Drugs/ScienceResearch/UCM578588.pdf. Accessed November 30, 2019.