To screen or not to screen: the importance of early detection of pectus excavatum

The currently most widely accepted etiologic hypothesis for pectus excavatum attributes the condition to abnormalities in the structure, function, and/or biomechanical properties of the costal cartilage (1). While a strong genetic component has been suggested, more than half of cases occur sporadically (1,2). In a recent study, Wang et al. [2024] explored pathophysiological mechanisms of pectus excavatum from a metabolic perspective, employing metabolomic and lipidomic analyses to identify biomarkers for (I) screening and (II) early detection (3,4).

Currently, no universal screening program exists for the detection of pectus excavatum biomarkers in the general population (5,6), and the benefits of such an approach remain uncertain. Inodole-3-acetaldehyde has been proposed as a potential biomarker for early detection and can be measured through high-performance liquid chromatography-mass spectrometry of serum samples. However, a venipuncture to obtain a serum sample is often experienced as rather unpleasant by a very young patient population and is perhaps only justifiable if the screening is contributory to the treatment of pectus excavatum. An alternative, less invasive tool to be considered would be the use of three-dimensional optical imaging, although currently these devices are not readily available at primary care centers. However, its use for early detection is not as straightforward as it would seem since a clear definition and cut off criteria to diagnose the deformity are still lacking which can lead to significant inter and intra-observer variability (7). Furthermore, there are several factors which can affect the external depth of the deformity, for example pectoralis major muscle tor breast tissue. Thus the use of biomarkers may be more appropriate for early detection, however the optimal cut-off value to reach a desirable sensitivity and specificity remains to be elucidated in future sufficiently powered research. Next, one must decide whether to implement universal or targeted screening (8,9). Although universal screening is preferable in most cases as it leads to high detection rates, targeted pediatric screening of only children with an emaciated appearance seems a better fit, considering the relatively low incidence rate of the deformity. Furthermore, as pectus excavatum is often detected after the first growth spurt, there is a chance that patients included in the “non-pectus excavatum” group in the study by Wang et al. [2024] will still develop the deformity at a later age since more than half of the researched patients were under the age of 5 years (3). Consequently, it remains unclear whether indole-3-acetaldehyde is a universal biomarker for all pectus excavatum cases or if it specifically applies to early-onset forms, which are thought to have a stronger genetic basis (10). Targeted genetic screening for these subpopulations could be a valuable addition to the diagnostic process, although the added value is debatable when the deformity is already apparent on visual examination. Additionally, the study authors do not specify how “healthy controls” were defined, as no inclusion or exclusion criteria were provided for this group. Predefining exclusion criteria such as comorbidities, any signs of pectus excavatum on examination, or a familial history of pectus excavatum or connective tissue disorder does however not prevent that any of the “healthy controls” develop pectus excavatum spontaneously during puberty and can thus still influence the results. Thus, before indole-3-acetaldehyde can be considered for clinical screening, further validation studies are required, followed by cost-effectiveness analyses. These should incorporate not only hospital expenditures but also patient and societal costs relative to quality-adjusted life years (QALYs) gained, as has been conducted for other neonatal screening programs such as those for amblyopia or hearing loss (11,12). Given that implementing such screening programs could impose significant societal costs without clear evidence of clinical benefit from early detection, the necessity of widespread screening remains uncertain.

As with most population-based screening programs, early detection and monitoring of pectus excavatum using indole-3-acetaldehyde, as proposed by Wang et al. [2024], is hypothesized to facilitate timely intervention and improve patient outcomes (3). However, this assumption is debatable, as most clinicians involved in pectus excavatum care agree that for straight-forward cases, 12 years of age is the youngest age at which a surgical correction should be performed, though some experts perform the correction at a younger age (13). Early detection at a younger age (i.e., <12 years old) in most cases will not affect the operative treatment plan of pectus excavatum but could result in a non-operative treatment through vacuum bell therapy. Studies show that vacuum bell therapy results in excellent correction in younger patients (i.e., between 8–12 years old) with mild deformities, which favors timely introduction of this non-operative treatment (14-16). It is questionable, though, whether a young patient population would be able to adhere to a strict treatment plan as is necessary for successful vacuum bell therapy- especially in the absence of a prominent deformity or (debilitating) symptoms. Wang et al. [2024] also suggest that current treatments may eventually be supplanted by pharmacological interventions that alter the gut microbiota (3). Furthermore, future research could elucidate if biomarkers could determine the physiological impact of pectus excavatum and thus provide information on the benefit of surgical correction. The initial steps taken in the exploration of the etiologic mechanism of pectus excavatum at the metabolic level, may provide a foundation for this future research for which the authors should be commended.

Besides the implications of a screening program, early detection of symptomatic disease in patients with pectus excavatum may be more beneficial in current clinical practice and should not be overlooked. At present patients are most often referred when the deformity is clearly visible on physical examination and leads to debilitating symptoms. Timely recognition of the deformity by primary care professionals is crucial to this process, however previous research has shown that the visual diagnosis of pectus excavatum yields considerable inter- and intra-observer disagreement (7). Once the deformity is recognized and the patient is referred the minimally invasive repair of pectus excavatum has widely been accepted as the standard approach in children and young adults. However, in the adult population the rigidity of the chest wall makes the procedure more difficult and chronic pain is seen more often as a postoperative complication (16-20). Thus, clear benefits can be obtained from timely recognition and increasing awareness amongst primary care professionals could aid in this process (21).

Wang et al. should be commended for their efforts in elucidating a novel etiologic mechanism for pectus excavatum at the metabolic level, as their findings suggest a potential metabolic biomarker for early detection. Their study highlights the need for a deeper understanding of the condition, which may inform optimal timing of intervention and contribute to the development of new treatment strategies. However, the implementation of this biomarker as a universal screening tool remains debatable, as the societal costs of screening for an asymptomatic deformity likely outweigh the potential health benefits. Therefore, the primary focus should remain on increasing awareness of pectus excavatum among healthcare professionals and ensuring timely referral to specialized pectus centers.

Acknowledgments

None.

Footnote

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