To Be (an Exacerbation), Or Not to Be?

This post was written by Michael W. Hess, MPH, RRT, RPFT

“Is it a bad day? Or is it an exacerbation?”

That question may not have the same ring as a Shakespearean soliloquy, but it is certainly closer to the front of most clinician’s minds when dealing with COPD. It has also largely been a question with no very definitive answers. Treatment recommendations have long held that early intervention in exacerbations is the key to minimizing further tissue injury (not to mention a hospital admission). At the same time, those recommendations also tell us that symptoms can vary widely from person to person and from day to day. How can clinicians tell the difference between an early intervention and an unnecessary one?

The answer may finally be on the horizon. Along with the other major paradigm shifts in the COPD world, 2023 brought the beginnings of a new framework to define and manage exacerbations. Known as the “Rome Proposal,” this new algorithm was technically published in late 2021 but really began to take hold after inclusion in the 2022 GOLD Report.

WHEN (NOT) IN ROME

The Rome Proposal is the product of a year of discussions, literature reviews, and analysis from some of the world’s leading COPD minds.1 They were originally intended to meet in Rome, Italy in January 2020, but that meeting was one of the earliest cancellations of the COVID pandemic. The group’s primary goal was to standardize the definition and evaluation of COPD exacerbations using objective measures. Previous attempts to grade the severity of an exacerbation were based almost exclusively on subjective measures like a person’s perception of their symptom burden. Symptoms are also not always tied to the physiological mechanisms at play during an exacerbation, potentially leading clinicians down incorrect pathways and possibly preventing them from detecting more serious issues during the course of treatment.

The result was a consensus document proposing a new “conceptual model” of a COPD exacerbation, a consensus definition, and a proposed severity classification scale. It is important to note that the algorithm does NOT make specific recommendations based on severity (unlike other aspects of the GOLD strategy). Instead, it is up to clinicians themselves to initiate the best therapies available to treat the underlying cause of the exacerbation (and hopefully relieve symptoms at the same time).

WHAT’S IN A NAME?

The foundation of the Rome Proposal is the new definition of an exacerbation:

In a patient with COPD, an exacerbation is an event characterized by dyspnea and/or cough and sputum that worsen over 14 days, which may be accompanied by tachypnea and/or tachycardia and is often associated with increased local and systemic inflammation caused by airway infection, pollution, or other insult to the airways.

At first glance, that may not appear to be all that groundbreaking. However, the definition now encompasses all the symptoms that may prompt someone to seek medical attention while maintaining focus on one of the key culprits of worsening dyspnea: local and systemic inflammation. By highlighting inflammation as an underlying process of exacerbations, the definition sets the stage for measuring inflammatory markers to assess severity. Also, 14 days may seem a rather long time to help in clinical decision-making, especially as 90% of exacerbations were found to hit their peak within 5 days of the initial worsening. The group decided to use the 14-day window to account for a fuller range of exacerbation causes. For example, some people with COPD do not reach an exacerbation state for up to 10 days after exposure to rhinovirus. The defined window also is expected to provide more insight into how long it takes an exacerbation to resolve, which could be a future mechanism to evaluate the relative efficacy of treatments.

SEVERE EXACERBATION WATCH

The team found that current methods of grading exacerbation severity were driven mostly by looking at health care utilization retrospectively. Given that health care resources can vary greatly around the world, this makes it tough to compare outcomes. The group’s efforts found a total of 21 potential objective measures to determine severity, which were eventually narrowed to six in the final consensus:

• Dyspnea (measured by the visual analog scale used for subjective pain)
• Respiratory rate (in breaths per minute)
• Heart rate (in beats per minute)
• Resting oxygen saturation (on ambient air or the patient’s usual prescription)
• Hypercapnia (measured via arterial blood gas sample)
• C-reactive protein (a measure of inflammation)

The team then established that exacerbations would be considered “mild” unless three of the measures were found to be outside certain limits. For example, if a patient presented with symptoms mentioned in the definition, a heart rate of at least 95, respirations above 24, and a CRP greater than 10, that would be considered a moderate exacerbation. Severe exacerbations were defined as an ABG sample showing hypercapnia with a pH less than 7.35 (or, for you respiratory therapy students out there, an uncompensated respiratory acidosis).

SUMMARY

The authors of the Rome Proposal are the first to point out that while this new definition handles many of the shortcomings of current exacerbation definitions, it is not yet a finished product. If nothing else, it must be validated in several populations. A single-center review published this year found that most exacerbations requiring hospitalization (usually considered severe) were actually moderate, and some were even mild.² That group found that the Rome parameters may help differentiate between types of exacerbations and predict mortality, but one study does not a validation make. However, we now at least have a starting point to guide research that will allow us to give our patients more definitive answers. That is, of course, the stuff dreams are made of.