Discussion
In young adults referred to our center for evaluation of pectus, we
found most have normal resting lung volumes, flows and normal aerobic
fitness. Among those with abnormal PFT patterns, most were mild and were
not associated with increased symptomatology, reduced aerobic fitness,
or magnitude of the pectus defect compared to patients with normal
patterns. Analysis of ventilatory responses during maximal exercise
revealed a pulmonary limitation in less than 3% of patients. Taken
together, we interpret these results to indicate that the pectus chest
wall deformity found in most pectus patients does not directly lead to
dyspnea or pulmonary limitations with exercise.
Obstruction was the most common abnormal pattern on PFTs identified in
10.7% of all referrals tested. This prevalence is higher than Lawson’s
prior study of 218 pectus patients where obstruction was reported in
less than 2%25. Lawson used a more stringent criteria
for obstruction of a FEV1/FVC of <67% which
likely explains the discrepancy between our studies. In a study of over
3,000 young adults in the general US population using a similar
definition of obstruction to ours the prevalence was
10.1%26. Overall, these findings suggest an
obstructive pattern in pectus is similar to what would be expected from
the general population.
Using both spirometry and plethysmography criteria we identified a
restrictive pattern in 7.5% of referrals. Lawson reported 14% of
pectus patients exhibited a restrictive pattern using only spirometry
criteria25. However, using spirometry without
plethysmography has been shown to have a low predictive value for
restriction and overestimates the incidence. Studies of spirometry with
matching plethysmography in adult PFT labs reveal approximately 50% of
restrictive patterns on spirometry have normal TLC on
plethysmography22,27. Applying this correction to
Lawson’s data would reduce the prevalence of restriction to 7%,
mirroring our findings. Both Lawson’s and our data suggest that the
prevalence of restrictive patterns in pectus is higher than would be
expected from the general population. A longitudinal study in Austria of
nearly 10,000 people in the general population using both spirometry and
plethysmography found a prevalence of restriction of 0.9% with no
restrictive patterns identified among those under 18 years of
age28.
The NSVL is an often-unrecognized distinct PFT pattern, which has not
been previously reported in prior pectus studies. The NSVL has not been
shown to associate with any specific clinical phenotype and can be found
in patients with a variety of underlying respiratory disorders including
asthma, chronic obstructive pulmonary disease, interstitial lung disease
and obesity29. Adult PFT laboratories report the
prevalence of NSVL pattern in 6.6% to 15% suggesting our finding of
NSVL in 7.5% of referrals may not represent a unique underlying
pathology21,29,30.
While the majority of CPET studies were classified as having normal
fitness, the average VO2 peak was 89% of predicted. Our
findings are consistent with several prior reports CPET studies in
pectus patients which demonstrate mild but significant reductions in
mean VO2 and O2 pulse values when
compared with either normative standards or age-matched
controls5,7,31,32. Findings from these studies and
ours thus support a physiologic impairment with exercise is likely in
some pectus patients.
Using scatterplots, we demonstrate a minor inverse association between
the correction index and both the TLC and FEV1. The
finding of lower lung volumes with a more extensive chest wall deformity
was also reported by Lawson who noted the likelihood of a restrictive
pattern was four times higher for pectus patients with a Haller index of
seven25. Multivariate analysis also demonstrated a
higher correction index and lower FEV1 were associated
with reductions in VO2 peak. Thus, the association of
both a lower VO2 and lower resting lung volumes with
more severe pectus may suggest a pulmonary limitation from a restrictive
defect contributes to the high rate of dyspnea or lower mean
VO2 peak in the pectus population. However, despite a
high number of patients with severe pectus, we identified a restrictive
ventilatory limitation during exercise in only six subjects. There was
no relationship between either the BR or Vt/IC with the correction index
(Figure 3) suggesting there are no limitations in the expansion of tidal
volume breathing during maximal exercise with more severe pectus
defects. Multivariate analysis also demonstrated peak
VO2 was positively associated with a higher Vt/IC and
inversely associated with the BR (Figure 4). These findings demonstrate
patients with pectus can appropriately increase their tidal volume to
achieve higher VO2. And there were no differences in the
mean BR or Vt/IC between pectus referrals with normal or abnormal PFT
patterns (Table 2) suggesting a resting ventilatory limitation was not
associated with limitations in tidal volume expansion with exercise.
Our finding in this study of a stronger correlation in the Vt/IC with
VO2 peak in females over males suggests females may have
greater effective ventilatory expansion of their tidal volume during
maximal exercise. We previously demonstrated that females with pectus
have significantly deeper chest wall deformity as represented by higher
pectus indices and higher frequency of chest pain and dyspnea on
exertion than males33. However, females have
significantly increased VO2, O2 pulse, a
higher breathing reserve than males, and right and left ventricular
ejection fraction greater than males. The mechanism for these findings
is unclear. One theory postulates females may have a more compliant
chest wall which thereby allows less fixed cardiac compression and a
more minor degree of cardiac impairment33.
We found 64% of pectus patients reported dyspnea on exertion, a finding
almost identical to Kelly’s 63% in a prospective observational study of
327 pectus patients34. Prior studies in adolescents
report an overall prevalence of dyspnea with exertion ranging from 7%
to 14% suggesting individuals with pectus experience greater dyspnea
symptoms than would be expected in the general
population35,36. In our study, among the those
reporting dyspnea on exertion nearly three-quarters had normal CPET, and
dyspnea was not associated with a reduced VO2 by
multivariable linear regression modeling. These results suggest dyspnea
in many pectus patients is likely caused by mechanisms other than
reduced oxygen delivery during exercise. Prior studies in adolescents
presenting with dyspnea collectively report the most common cause is
normal physiological limitation, a condition believed to be caused by an
excessive sensation of the perceived work of breathing with increased
ventilation during exercise37,38. Other common causes
include vocal cord dysfunction (VCD), exercise-induced bronchospasm
(EIB), exercise-induced hyperventilation and deconditioning. We did not
assess directly for EIB as lung function was not performed after
exercise nor were patients exercised on an EIB protocol. VCD was also
not directly assessed as we did not perform laryngoscopy during
exercise, however the incidence is likely low as stridor was not
auscultated during exercise and flattening of inspiratory loops was not
observed during exercise.
A little over one-quarter of pectus referrals reporting dyspnea
demonstrated reduced fitness. Deconditioning is reported in 10-23% of
adolescents with dyspnea and may be a significant contributing factor to
dyspnea in pectus38,39. However several reports
demonstrated cardiac filling in pectus is reduced in some patients as a
result of compression by the displaced sternum on the right heart
chambers or torqueing of the great vessels, thereby constraining
increases in cardiac output during vigorous
exercise3-5,40. Limitations of CPET in identifying
precise mechanisms for exercise intolerance include specific response
patterns are rarely pathognomonic and indirectly informative regarding
the central hemodynamic responses to exertion. Further studies including
assessment of cardiac MRI endpoints will be important to differentiate
if dyspnea with reduced VO2 peak in pectus is from
direct anatomic compression of cardiovascular structures versus
deconditioning or other mechanisms.
We conclude that in most pectus referrals to our center, respiratory
limitations during maximal exercise are rare and an unlikely cause for
the observed high the rates of dyspnea on exertion or reduced aerobic
fitness. Resting lung volume measurements on PFTs were associated with
the anatomic degree of pectus severity but not symptoms or physiologic
outcomes measured during maximal exercise testing. Future prospective
studies enlisting age and sex-matched controls are needed to better
understand the apparent male-female differences, the underlying
mechanisms for the high rates of symptomatology and inform under which
conditions there are meaningful physiologic benefits for surgical repair
of the defect.