Is the end near for surgical and transbronchial biopsies? Challenges in the pediatric workforce; Cascade testing in PAH; and more ...
Pulmonary vascular disease
Cascade testing in PAH: Is there a role?
Pediatric guidelines for pulmonary arterial hypertension (PAH) recommends genetic screening as a part of the evaluation for the newly diagnosed, with expansion to first-degree relatives as indicated. Currently, this is not mandated, and implementation is variable. In adults, genetic screening is not routinely offered, and family screening is rare. This reflects a lack of definitive guidelines (Abman SH, et al. Circulation. 2015:24;132[21]:2037-99). However, it is intuitive that if carriers are not identified by screening, they will come to attention after pulmonary vascular disease burden causes symptoms and affects outcomes.
Cascade testing is a screening methodology that is used in heritable cancers (George RM, et al. Genet Couns. 2015;24[3]:388-99). In cascade testing, identification of an index case prompts screening of at-risk family members. If these relatives are positive for mutations, the cycle is repeated (cascaded) to their immediate relatives, allowing for targeted screening. This approach is especially effective in genetic mutations that are inherited in an autosomal dominant fashion, such as in BMPR2 gene mutation. Cascade testing is an effective way to capture relatives who would otherwise be overlooked.
Unfortunately, in the United States, the cost of genetic testing is a significant obstacle to universal implementation. A new diagnosis of heritable pulmonary arterial hypertension (HPAH) is often followed by a multigene panel with costs exceeding $1000 and may prompt subsequent targeted testing resulting in additional expense (Chung WK, et al. Can J Cardiol. 2015;31[4]:544-47). Furthermore, a positive mutation detected on screening is not definitively associated with disease due to variable penetrance (Morrell NW, et al. Eur Respir J. 2019;53[1]:1801899]. As such, mass screening strategies are not recommended. The recent DELPHI-2 study [Montani D, et al. Eur Respir J. 2021;58[1]:2004229) have demonstrated that genetic screening is impactful in families with HPAH. A genetic screening algorithm should be considered, and cascade testing could be a cost-effective targeted approach.
Sandeep Sahay, MD, MSc, FCCP: Steering Committee Member
Jean M. Elwing, MD, FCCP: Chair
Pulmonary physiology, function, and rehabilitation network
Physiological benefits of awake proning: Its role and relevance in the COVID-19 pandemic
The advent of the COVID-19 pandemic has put a significant strain on the health care systems and critical care services across several countries, including the United States. Amidst this, several concerted efforts to reduce the need for mechanical ventilation has resulted in the emergence of awake proning as a strategy to improve oxygenation, which has been instituted in critical care units, in-patient settings, as well as in EDs. Although the evidence on this strategy has been vastly limited to case series and observational studies, several societies have incorporated awake proning as an initial management strategy in hypoxemic respiratory failure within their clinical guidelines (Chalmers JD, et al. Eur Respir J. 2021;57:2100048; Koeckerling D, et al. Thorax. 2020;75:833-4) and consensus statements (Nasa P, et al. Crit Care. 2021;25:106).
Physiological benefits of awake proning include improvement in ventilation-perfusion matching secondary to relative increase in ventilation in dorsal nondependent areas in the setting of higher density of perfusion within these units, thus reducing shunt and, hence, improving oxygenation. Other physiological mechanisms include homogenization of transpulmonary pressures, reduction of ventilator-induced lung injury (VILI) or patient self-inflicted lung injury (P-SILI), and possibly lung injury from pendelluft (Telias I, et al. JAMA. 2020;323[22]:2265-67).
A recent meta-trial involving randomized controlled trials done across six countries compared prone positioning with standard care in patients with hypoxemic respiratory failure (defined as SpO2/ FiO2 < 315 and on high flow oxygen therapy) showed a reduced incidence of treatment failure and need for intubation without any signal of harm; although no mortality benefit was reported (Ehrmann S, et al. Lancet Respir Med. 2021 Aug 20;S2213-2600(21)00356-8). The number needed to treat to prevent one intubation was 14. While promising and reinforcing the safety of this relatively easy maneuver, several questions remain—which patients would benefit the most? Can it be applied within general wards safely? Does institution of awake proning delay intubation rates with consequent worse outcomes? Several ongoing (NCT 04402879) and completed studies (NCT 04383613 and NCT 04350723) may shed light on these important questions (Weatherald J, et al. Lancet Respir Med. 2021 Aug 20;S2213-2600[21]00368-4).
Sujith Cherian, MD, FCCP: Steering Committee Member
