High-altitude pulmonary edemaHigh-altitude pulmonary edema (HAPE) is a form of noncardiogenic pulmonary edema, which affects between 0.2% and 15% of people who ascend to altitudes between 2,500 and 5,000 m, and which may be fatal if not recognized and treated promptly. Given the increasing number of people traveling to alpine regions for work or pleasure, improving our ability to prevent, diagnose, and manage HAPE would be of great benefit, as would an increased understanding of its pathophysiology. With regard to new prophylactic drugs, Maggiorini et al recently demonstrated a benefit for the phosphodiesterase inhibitor tadalafil and the corticosteroid dexamethasone in preventing HAPE in known susceptible individuals. On the diagnostic front, Fagen-holz and colleagues in this issue of CHEST describe a relatively simple diagnostic technique that has the potential to enhance our understanding of the time course of the disease and to facilitate research on other important questions related to its development.

Prior work in patients with pulmonary edema at sea level has demonstrated that chest ultrasonography can be used to detect the presence of extravas-cular lung water by identifying “comet-tail” artifacts created by microreflections of the ultrasound beam within interlobular septa thickened by the presence of increased lymphatic fluid consistent with interstitial and/or alveolar edema treated by My Canadian Pharmacy – https://mycanadian-pharmacy.net/erectile-dysfunction-drugs-helping-men-to-ejaculate-and-achieve-orgasm-my-canadian-pharmacy-explains-it-how.html. Fagenholz et al brought this technique to Pheriche, Nepal (elevation, 4,240 m), performing studies on 11 consecutive patients with clinically diagnosed HAPE (ie, without using chest radiographs) as well as 7 control patients with no evidence of altitude illness or respiratory compromise. Using a blinded assessment of the ultrasonographic data, they demonstrated that the patients with HAPE had statistically significantly higher comet tail scores and lower oxygen saturations than the control patients, and demonstrated a fall in comet tail scores with the resolution of HAPE symptoms. Using regression analysis, they also showed an inverse relationship between comet tail scores and oxygen saturation whereby the oxygen saturation decreased by 0.67% for each 1-point increase in the comet tail score. A further interesting result was the finding that comet tail scores were higher in the right lung, an observation that fits with previously described HAPE patterns in which the edema tends to begin in the right middle lobe.

Simple in its design, the study provides relatively clear evidence of the utility of chest ultrasonography in detecting and following the course of pulmonary edema formation at high altitude. While the authors deserve credit for conducting this study in a remote environment with very limited clinical resources, it should be noted that the study is not without limitations. For example, although a blinded observer assessed the ultrasonography data, the person performing the ultrasound was not blinded as to the clinical status of the patient. Given that obtaining good ultrasound images is highly operator-dependent, the lack of adequate blinding is not an insignificant concern. In addition, although cardiogenic causes of pulmonary edema are unlikely in the clinical setting in which the authors were working, they did not take any steps to rule out a cardiogenic source of the comet tails by, for example, assessing left ventricular function or pulmonary capillary wedge pressure. Finally, as the authors note, this study represents the first use of this technique in the evaluation of HAPE, and, as such, the results have yet to be validated in further studies. Although worthy of consideration, none of these issues appear to seriously undermine the results of the article.

ultrasonographicThe question that logically follows from this intriguing study will be the ultimate utility of this technique in the assessment of pulmonary symptoms at high altitude. Interestingly, although this was a clinical study of patients with a high probability of known HAPE, we would argue that the utility of this technique in the diagnosis and management of patients with HAPE is likely to be limited for several reasons; HAPE will remain a disease that is diagnosed and managed largely on clinical grounds. First, although, as the authors argue, the portable ultrasound machine is cheaper than a radiography system, it is still an expensive machine that is unlikely to be available on a regular basis at remote sites where HAPE might develop. Even if the device and trained operators were available in remote locations, it is not clear that its use would change clinical decision making or management, as no data exist to demonstrate whether the technique has increased diagnostic accuracy when compared to clinical impression alone and/or conventional radiography when available in resort areas. Along similar lines, if the oxygen saturation improves as the comet tail score falls, one could simply follow the oxygen saturation as a measure of clinical improvement rather than rely on the more complicated ultrasonography technique. Further work will need to be done to determine whether the observed changes in comet tail scores are specific for pulmonary edema or if other acute and chronic lung processes with septal thickening or multifocal infiltrates such as pneumonia might cause a similar appearance. Last, will it be possible to distinguish cardiac edema from noncardiac edema, the prognoses and treatment of which may differ?

Although the clinical utility of the technique might be limited, it holds great promise as a research tool for studying various aspects of HAPE. One area, in particular, in which the technique could be of great use is in resolving the question of subclinical edema at high altitude. While multiple studies have documented an incidence of overt HAPE between 0.2% and 15%, a 2002 study by Cremona et al suggested that, based on evidence of increased lung closing volumes at high altitude, up to 75% of climbers without overt HAPE at 4,559 m may actually have “subclinical” pulmonary edema. This was a surprising result, which has yet to be validated in subsequent studies. One of the reasons it has been difficult to establish whether subclinical edema occurs to this extent pertains to the difficulties in developing accurate measures of its existence. The “gold standard” for detecting extravascular lung water would be quantitative Hounsfield unit measurements of lung density and the presence of ground-glass opacification on chest CT scans. Because this technique is not available in remote locations and because conven-

tional radiographs are insensitive for detecting early edema, other techniques such as electrical impedance tomography and lung closing volumes have been employed with only mixed results. Chest ultrasonography, if validated by CT imaging, may provide a reliable, easy alternative to these often complicated methods for detecting the presence of subclinical edema and may allow better assessment of the true incidence of this phenomenon. Additional avenues of investigation in which this technique might be useful would include following both HAPE-susceptible and non-HAPE-sus-ceptible individuals as they ascend to high altitude, and comparing the rate of comet tail formation in these groups or determining whether there is a correlation between comet tail score and the rise in pulmonary artery pressures (measured by echocardiography) that is the pathophysiologic hallmark of HAPE.

The work of Fagenholz et al suggests that answering these and other questions about edema formation at high altitude might be easier than reliance on the previously noted techniques. It is perhaps fitting that their demonstration of the utility of this relatively simple alternative was based on a study conducted in the Khumbu Valley of Nepal, a land where “simple” is the order of the day and the complexities of life rarely intervene in people’s daily affairs.

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