Discussion
Due to resource limitations, other differential diagnosis like pneumonia
could not be ruled out with a guarantee in any of the cases. However,
many symptoms, examination findings, young age, absence of significant
past medical history more importantly, ultrasonography findings
suggesting pulmonary edema along with rapid improvement in symptoms and
oxygen saturation within a very short period of oxygen in all three
patients make a strong case favoring the diagnosis of HAPE.
Certain preventive measures can be applied to minimize the modifiable
risks of HAPE: gradual ascent (via vascular remodeling) [2, 8, 9]
and Nifedipine (via reduction in pulmonary artery pressure) [2, 7, 8,
9] and with moderated exertion. However, certain non-modifiable risk
factors, especially those attributable to higher pulmonary artery
pressure [12], stronger hypoxic pulmonary vasoconstriction [12],
reduced nitric oxide [13], inappropriate sympathetic response
[13], congenital heart defects (e.g. patent foramen ovale) have
their own share of hidden role in causing HAPE. Hypoxic pulmonary
vasoconstriction response primarily functions to reduce the
ventilation-perfusion mismatch created by a diseased lung segment. It,
however, also works as the main pathophysiological phenomenon behind
HAPE. In the background of individual risk factors, regional variability
in response to pan-hypoxia [14, 15, 16], and stress failure of
capillaries [1] makes some individuals more susceptible to this
non-inflammatory, non-cardiogenic exudative edema.[17]
Hypoxic vasoconstriction of some arteries shifts the pressure to other
arteries. Adaptation involves remodeling of such arteries over the
period of hours to days so that the downstream capillaries are protected
from damage due to redirected pressure. This remodeling usually gets
completed within 5 days. [5, 6, 18] However, few case reports,
including a case series of eight patients have described delayed onset
HAPE where symptoms began after 5 days. [19] While there is no clear
explanation for such a phenomenon, few hypotheses attribute the triggers
to risk factors related to individual physiological differences,
infection [20] and overexertion [21], which overcome the
protection provided by proper acclimatization. [19, 22] It can also
be hypothesized that individuals susceptible to delayed onset HAPE might
either have a slower pulmonary vascular remodeling process at high
altitude or have underlying congenital defects that could create a
physiological base where a single ‘push factor’ in the form of
infection, overexertion, etc. could trigger HAPE. The high recurrence
rate of HAPE in individuals with a history of HAPE further supports the
interplay of underlying individual risk factors. [23] Re-entry HAPE
among highlanders shows that the previously obtained adaptive features
can reverse upon migration away from the hypoxic high-altitude
environment. [24]
In our series, even though the first and the second case patients had no
evident features suggestive of respiratory infection; in the background
of their probable physiological susceptibility, overexertion led to a
rise in cardiac output and pulmonary artery pressure. The increase in
these two parameters probably served as a trigger for HAPE. [25]
Impairment of their alveolar ENaC channels in response to hypoxia and
hypothermia could have played a role as well. [26]
In our third case, preceding pulmonary injury due to infection probably
predisposed the affected lung towards HAPE. Pre-existing
ventilation-perfusion mismatch along with endothelial stress leading to
impaired fluid clearance must have played a significant role in the
development of HAPE isolated to a single lung.
In all three cases, POCUS has played an important part in the diagnosis.
It can provide an objective measure of a patient’s response to treatment
as in our third case. However, the correlation between clinical and
ultrasonography findings during the course of treatment needs to be
studied.
Conclusion :
Diagnosis of HAPE can get challenging when it deviates from the course
of its natural history. Association to over-exertion or respiratory
illness can contribute to such a phenomenon. The threshold for diagnosis
and treatment should be lowered in a resource-limited setting,
especially in young adults presenting with a dubious picture, who have
minimal risk factors for other acute lung diseases. POCUS is a great
asset for early diagnosis of HAPE in resource-limited settings. Its role
in HAPE monitoring needs to be explored further.