Reply to Finsterer: Why HAPE Was the Most Likely Diagnosis in This Case

The Authors Reply We thank Dr. Josef Finsterer for thoughtful comments on our case of high-altitude pulmonary edema (HAPE) on Mt. Fuji (1). We have addressed each point below: To further clarify our findings, we issued the following statement:

1. Differential Diagnoses

1-1. Pulmonary embolism (PE)

We agree that the authors' points regarding the differential diagnosis is important. However, we considered the possibility of acute PE to be low in this patient based on the following points: 1) The patient developed progressive dyspnea and hypoxemia within hours of staying at 3,250 m. After his descent, the patient was treated with systemic corticosteroids, antibiotics, and a vasodilator. His condition improved without anticoagulation therapy. This time course was more consistent with HAPE than PE. 2) A plain computed tomography (CT) scan at the time of admission showed no infiltration beneath the pleura and revealed no findings strongly suggestive of PE (2). 3) Owing to resource constraints at the facility, D-dimer test results were unavailable. As a pragmatic substitute, fibrin/fibrinogen degradation products were measured (3), which were not elevated. 4) Electrocardiography (ECG) showed sinus tachycardia only, without right-heart strain patterns.

1-2. Cardiomyopathy/Coronary heart disease

Cardiac disease is an important factor in the differential diagnosis. In this case, the brain natriuretic peptide elevation was mild (Table). This phenomenon can accompany severe hypoxemia and pulmonary hypertension during HAPE, and does not always result in left-sided failure (4). There were no clinical signs of congestion, and ECG showed sinus tachycardia without ST elevation. We note that “altitude cardiomyopathy” is not an established diagnosis; nevertheless, we explicitly state that acute coronary syndrome and cardiomyopathies were considered but were deemed unlikely based on the clinical-imaging-evolution triad. It should also be noted that the article cited by the author was retracted (5).

1.3 Neurogenic pulmonary edema (NPE)/HACE

The patient had no neurological symptoms (altered mental status, ataxia, or focal deficits) (6). In the absence of neurological signs, brain CT was not routinely performed. We clarified this rationale.

1.4 Coronavirus disease 2019 (COVID-19)

All patients presenting with respiratory failure during the COVID-19 epidemic period at our hospital, including this patient, underwent COVID-19 antigen or polymerase chain reaction (PCR) testing. The patient also tested negative for the COVID-19 antigen test.

2. Cyanosis

As noted by the author, the attending physician did not adequately assess for the presence of cyanosis upon arrival at the hospital. However, cyanosis is neither necessary nor sufficient for the diagnosis of HAPE. The reference cited by Finsterer proposed that at least two of the following symptoms, chest tightness or pain, cough, dyspnea at rest, and decreased exercise tolerance, are required for a clinical diagnosis, along with two of the following clinical findings: central cyanosis, rales/wheezes, tachycardia, and tachypnea (7). The patient met these criteria.

3. Follow-up and Bronchoscopy

We obtained follow-up imaging, which demonstrated complete resolution and highlighted this more prominently. We did not perform bronchoscopy because the working diagnosis and response to noninvasive therapy made an invasive procedure under severe hypoxemia unjustified.

4. Reference Values

We did not provide reference values. The primary purpose of Table is to describe the clinical status of the index patient. The main readership of this article is assumed to be clinicians and researchers who are well-versed in the general reference ranges for routinely used tests (e.g., hemoglobin, creatinine, C-reactive protein). For any findings considered clinically significant in interpreting these study results, we explicitly describe them and their implications in the Results and Discussion sections. Therefore, even without listing reference values in Table, we believe readers can fully understand which findings were considered “abnormal” and how they influenced the outcomes. Furthermore, the CARE guidelines require that “important tests and imaging findings be documented with sufficient detail for other physicians to interpret,” but do not require the inclusion of reference values (8).

We would like to express our renewed gratitude to Dr. Josef Finsterer for his thorough review and sincere hope that the medical community's understanding of HAPE will continue to deepen.

The authors state that they have no Conflict of Interest (COI).