Labored breathing pattern: an unmeasured dimension of respiratory pathophysiology

Introduction: Respiratory failure is a common organ failure syndrome in hospitalized patients1. Vital sign monitoring (like respiratory rate & oximetry) is a necessary aspect of risk stratification, but it is not sufficient. In one study of hospitalized patients, 46% of the patients had no significant vital sign change in the 24 hours before an unplanned intubation2. Therefore, clinicians must also monitor for physical diagnostic signs that link the appearance of breaths to respiratory instability. Many pathognomonic patterns of high-risk labored breathing have been described. For example, when rib-dominant breaths alternate with abdomen-dominant ones, the patient is said to exhibit respiratory alternans, a sign of inspiratory muscle overload3. However, the manual assessment of such signs lacks sensitivity, inter-rater reliability, and scalability4. We sought to (a) identify technologies that can measure labored breathing and (b) assess their readiness for clinical adoption by hospitals. Methods: We selected four well-established diagnostic signs of labored breathing: (1) respiratory rate variability, (2) recruitment of accessory muscles (upper-rib elevation by the scalene and sternocleidomastoid muscles), (3) Abdominal Paradox (rib-abdomen asynchrony), and (4) respiratory alternans (rib-dominant breaths alternate with abdomen-dominant ones). We systematically searched PubMed using pre-specified keywords corresponding to these four signs. We identified 2868 abstracts. Two reviewers independently screened each abstract to ensure that it reported on technology that quantified the diagnostic sign of interest. A third reviewer resolved any disagreements. We excluded 2423 articles with an abstract review and included 445 articles for full paper review. We excluded an additional 127 articles after full paper review, and we were unable to acquire 4 articles. We included the remaining 314 articles for analysis. Results: Quantification of labored breathing has been attempted for over 50 years; the earliest study included in our analysis was published in 1975. Over 30 different hardware configurations have been tried, either alone or in combination; but none of them has been validated as a comprehensive solution to measure all the four diagnostic signs that we studied. Despite enormous improvements in sensor technologies and computing capacity, the scale of investigation has not meaningfully increased since 1975. In the first decade of kinematic measurements (1975-1984), there average annual number of studies was 2.7 and the median sample size was 19. In the decade prior to our study (2013-2022), the average annual number of studies was 11.3 and the median sample size was 20. To this day, a majority of the studies are conducted in a specialized laboratories (73% between 2013-2022) rather than clinical practice settings. Most studies aimed to measure the construct validity of a technology (19%) or to describe kinematic distributions in specific clinical scenarios (77%). Rarely did studies attempt to quantify the predictive validity for a clinical outcome (4%). We did not find any clinical trial where a kinematics-based early warning intervention was tested. Conclusions: This study describes a major bottleneck in the translation of bedside diagnostic signs of high-risk labored breathing patterns into measurable physiomarkers of respiratory instability. Despite half a century of attempted measurement, the technology readiness level for clinical adoption remains low.