Background
The first human infections with avian influenza A (H7N9) associated with poultry exposure were reported in China in March of 2013[
1]. Although mild illnesses have been observed, more concerning are the presentations of severe respiratory failure that have occurred in most cases, of which approximately one-third have resulted in death. No evidence of human-to-human transmission has been found so far[
2]. However, a pandemic outbreak of this virus or other similarly lethal viruses such as MERS coronavirus or influenza A (H5N1) with rapid human-to-human spread would constitute a dire public health emergency.
Experiences with prior respiratory virus outbreaks[
3‐
5] have demonstrated that point-of-care lung ultrasound can assist in distinguishing between various acute respiratory pathologies such as pneumonia[
6], viral pneumonia[
3‐
5,
7], and acute respiratory distress syndrome[
8‐
10]. Point-of-care lung ultrasound may be a first-line diagnostic imaging alternative to chest X-ray early in the course of disease or CT scan in critically ill patients that cannot be moved[
11] and may be used repeatedly to monitor disease progression[
7] or resolution[
12] especially in pandemic conditions when time and resources are scarce or overwhelmed[
4].
Discussion
The development and description of point-of-care lung ultrasonography has been reviewed, and evidence-based recommendations for its use published[
11,
14]. Discrete ultrasonographic findings seen in our patients (B lines, confluent B lines, pleural effusion, and most specifically, small subpleural consolidations) have similarly been observed in other viral pulmonary infections such as measles, other influenza A subtypes (H1N1), and respiratory syncytial virus by multiple investigators around the world in pandemic and non-pandemic situations[
3‐
5,
7]. Our second patient had co-existing consolidated pneumonia based on the finding of lung consolidation and air bronchograms visualized by ultrasound[
6,
13].
These ultrasonographic findings can be investigated using a high frequency linear transducer as small subpleural consolidations as well as small pleural effusions can be missed with lower frequency curvilinear probes and cannot be visualized by chest X-ray[
4,
15,
16]. Larger footprint lower frequency curvilinear (up to 60 mm in length) or microconvex probes can be used to rapidly assess the extent of lung pathology, especially in patients with impending respiratory failure[
5,
15]. Interstitial syndrome on ultrasound is visualized as numerous B-lines (at least 3 per field of view)[
8,
11,
12]. Acute respiratory distress syndrome (ARDS) is seen as the predominant presence of confluent B lines ( at least >3 B lines per field) or white lung associated with pleural line abnormalities described as thickening (>2 mm) or coarsening, with few spared areas (observation of A lines)[
10]. Bacterial (consolidated) pneumonia is distinguished from viral (interstitial) pneumonia by ultrasonography visualized as lung consolidations with sonographic air bronchograms, typically larger than 0.5 cm in depth[
4,
5,
7,
16,
17].
Our cases were confirmed to have influenza A H7N9 by RT-PCR, where prior research efforts to characterize the diagnostic accuracy of these findings have been hampered by the lack of access to an appropriate or logistically feasible reference gold standard for viral pneumonia[
4,
5,
7]. However, it has been noted that these findings have very high interobserver reliability (Cohen's
K = 0.82)[
4] and can be detected early in the course of disease when chest X-ray may often be normal[
5]. Additionally, numbers of viral ultrasound findings have been shown to correlate with disease severity in admitted infants with viral bronchiolitis, with resolution of ultrasound findings as symptoms resolve[
7].
This high interobserver agreement in ultrasonographic findings may promote reduced practice variation in antibiotic or antiviral medication prescribing relative to chest X-ray for improved antibiotic or antiviral medication stewardship. In severe cases, point-of-care lung ultrasound may lead to efficient allocation of resources such as respiratory isolation rooms, ventilatory support, and ECMO. It is unclear if different virus types (e.g., H7N9 vs. H5N1 vs. H1N1 vs. RSV) manifest different patterns in viral lung ultrasonographic findings (relative numbers of B lines, confluent B lines, and small subpleural consolidations). Further investigation into these ultrasound patterns may allow distinguishing between different virus types on the basis of ultrasonographic findings[
18]. Autopsies of patients with influenza A (H5N1) virus infection have ‘shown diffuse alveolar damage with hyaline membrane formation, patchy interstitial lymphoplasmacytic infiltrates, bronchiolitis with squamous metaplasia and pulmonary congestion with varying degrees of hemorrhage’[
19]. Our second patient had similar findings on postmortem examination (Figure
3). We speculate that these interstitial infiltrates and pulmonary congestion would appear on ultrasound as B lines or confluent B lines (or white lung), with hemorrhage appearing as small subpleural consolidations similar to that observed in our cases and in other viruses.
From a practical and logistical viewpoint of managing large numbers of patients during a pandemic outbreak, point-of-care lung ultrasonographic evaluation can be performed more rapidly, efficiently, and cheaply than chest X-ray. During pandemic overcrowding from 2009 influenza A (H1N1), emergency department volumes quadrupled and waiting times for chest X-ray tripled from a median of 29 to 98 min, contributing to delays for all patients requiring imaging[
4]. With reported median lung ultrasound exam times of 6 min[
4], point-of-care ultrasound can be used to reduce ED congestion and is scalable by increasing numbers of portable ultrasound units with clinicians capable of performing lung ultrasound. For patients too critically ill to be transported for CT scan, point-of-care ultrasound is a feasible imaging alternative[
8]. A greater concern when evaluating children who are at risk for higher mortality from avian influenza A (H5N1) infection[
19] is that ultrasonography avoids radiation exposure that elevates future cancer risk when using chest X-ray or CT scan[
20,
21].
Our first patient had all of the sonographic findings (B lines, confluent B lines, small subpleural consolidations, spared areas, and pleural effusion) described for ARDS[
10] that were noted to be resolving on serial ultrasonographic examinations with clinical improvement. Our second patient had similar findings with ominous changes in the left upper lobe with normal aeration (A lines) initially, progressing to interstitial syndrome (B lines) or pulmonary congestion (Figure
2C,G) noted on serial lung ultrasounds prior to succumbing. These findings are similar to ultrasound findings described with other influenza A subtypes (H1N1 and seasonal), as well as other viral pulmonary infections[
3‐
5].
Conclusions
Clinicians with access to point-of-care ultrasonography may use these findings as an alternative to chest X-ray or CT scan. Lung ultrasound imaging may help guide triage of resources[
4] (e.g., respiratory isolation rooms, ventilators), medical decision-making[
5] (e.g. antivirals, antibiotics, fluid administration, or ECMO) and monitor disease progression or resolution with therapy, especially in resource scarce settings or situations such as future respiratory virus outbreaks or pandemics[
19,
22].
Consent
Written informed consent was obtained from the patient (for case 1) and the patient's next of kin (for case 2) for publication of this report and any accompanying images.
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Competing interests
The authors declare that they have no conflicting or competing interests.
Authors’ contributions
NWT, CWN, KLM, and JWT participated in the conception and design of the study. NWT and CWN did the acquisition of data. NWT, CWN, KLM, and JWT participated in the analysis and interpretation of data. NWT, CWN, KLM, and JWT drafted the manuscript. NWT, KLM, and JWT participated in revising for critically important intellectual content. JWT supervised in the overall process. All authors read and approved the final manuscript.