Interventional chest and diagnostic procedures
Impact of COVID-19 pandemic in patients with non-advanced LC
The COVID-19 pandemic has challenged the way we screen for, diagnose, and treat lung cancer.1, 2 Knowing that these patients are at higher risk of respiratory failure, and that COVID-19 causes poor outcomes in cancer patients,1,3,4 valid concerns regarding viral transmission to patients and health-care workers have hampered the expedited care this population needs.
In recent months, efforts to manage the pandemic have been herculean. With the goal of limiting transmission, expert panels have offered guidance including limiting access to medical facilities, decreasing aerosolizing procedures, and prioritizing curative treatments.2,5 In general, lung cancer screening should be delayed, and patients with highly suspicious localized pulmonary lesions could receive empiric regimens, surgery, or stereotactic radiotherapy.1,3-5
The conundrum occurs when diagnostic bronchoscopy is required for staging, acquiring tissue for targeted therapy, or a moderate-risk pulmonary nodule with indeterminate PET-CT and/or high-risk for CT-guided biopsy. Thoughtful balancing of risks and benefits depends on patient comorbidities, hospital resources – such preprocedural COVID screening, adequate protective personal equipment- and rate of local viral prevalence.6,7 Delaying diagnosis and staging could lead to progression of cancer and preclude curative or adjuvant therapy for appropriate candidates. Furthermore, we should not dismiss the appalling psychological impact of delayed care on our patients.
While the pandemic continues and challenges arise in the care of patients with lung cancer, the value of a multidisciplinary input and individualized care cannot be overstated, with focus on providing the best care possible while both minimizing transmission and increasing the chances of acceptable outcomes.
Jose De Cardenas MD, FCCP – Steering Committee Member
Abdul Hamid Alraiyes MD, FCCP – Steering Committee Member
1.. doi: 10.1016/j.chest.2020.04.020.
2.. doi: 10.1136/esmoopen-2020-000765.
3.. doi: 10.1016/S1470-2045(20)30096-6.
4.. doi: 10.1200/OP.20.00286.
5.. doi: 10.1016/j.jtho.2020.05.001.
6.. doi: 10.1097/LBR.0000000000000681.
7.. doi: 10.21037/jtd.2020.04.32.
Pediatric chest medicine
FDA strengthens the boxed warning for montelukast
Early this year the Food and Drug Administration (FDA) updated the boxed warning for montelukast (Singulair), related to the potential for serious mental health side effects, such as agitation, aggressive behavior, depression, hallucinations, and suicidal thoughts and actions. Since its approval in 1998, montelukast is part of the therapeutic approach for persistent asthma in children age 1 year and older, allergic rhinitis from 6 months and older, and exercises induced bronchospasm in children age 6 years and older. In 2018, around 2.3 million children younger than 17 years received a prescription for montelukast.
The FDA reviewed data from their Sentinel System comparing children receiving montelukast vs inhaled corticosteroids, and this study failed to demonstrate significant increased risk of hospitalized depressive disorders, outpatient depressive disorders, self-harm, or suicide. However, a focused evaluation by the FDA of suicides identified 82 cases of completed suicides associated with montelukast, and 19 of these cases were in children younger than 17 years of age.
Post-marketing case reports submitted to the FDA, published observational and animal studies were evaluated along with the Sentinel System study that led to the new recommendations.
Finally, on March 4, 2020, the FDA updated the Singulair®/montelukast black box warning, focusing on the importance of advising patients and caregivers about the potential for serious neuropsychiatric side effects and advice to immediately discontinue use if symptoms occurred. The warning contains a strong recommendation to reserve use of Singulair®/montelukast to patients with allergic rhinitis who have an inadequate response or intolerance to alternate therapies.
Endy Dominguez Silveyra, MD - Fellow-in-Training Member
1. FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis., March 4, 2020.
2. Neuropsychiatric events following montelukast use: A propensity score matched analysis., Sept. 27, 2019.
Pulmonary physiology, function, and rehabilitation
The happy hypoxic
In early December 2019, the novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified. Over the ensuing months, SARS-CoV-2 would cause a wide range of pulmonary symptoms from cough and mild shortness of breath to acute respiratory distress syndrome (ARDS) with severe hypoxia that puzzled intensivists worldwide.
One such mystifying presentation was finding patients with critically low oxygen levels who did not appear to be short of breath. This concept was dubbed “happy or silent hypoxemia.” Novel mechanisms of the SARS-Co-V-2 virus on the respiratory system have been proposed to explain this paradox, but recent literature suggests that foundational pulmonary physiology concepts can explain most of these findings.1
Breathing is centrally controlled by the respiratory center in the brain stem and is influenced mainly by dissolved carbon dioxide and pH.2 Hypercapnia is, therefore, a powerful stimulus to breathe and increase minute ventilation. It can cause dyspnea if this demand is not met.3
Hypoxia, on the other hand, is less powerful and does not evoke dyspnea until the PaO2 drops below 60 mm Hg.4 Hypercapnia potentiates this response: the higher the PaCO2, the higher the hypoxic response. Patients with a PaCO2 of 39 mm Hg or less may not experience dyspnea even when hypoxia is severe.1
Other possible explanations for silent hypoxemia include the poor accuracy of the pulse oximeter for estimating oxygen saturation of less than 80%,1 especially in the critically ill5 and the leftward shift of the oxygen dissociation curve due to fever, making the oxygen saturation lower for any given PaO2.1
In conclusion, the clinical management of COVID-19 pneumonia with a broad range of clinical features presents many unknowns, but it is reassuring to find an anchor in good old pulmonary physiology concepts.5
It is back to the basics for us all and that might be a good thing.
Oriade Adeoye, MD – Fellow-in-Training Member
1.. doi: 10.1164/rccm.202006-2157CP.
2.. doi: 10.1164/rccm.201903-0596SO.
Pulmonary vascular disease
COVID-19 and pulmonary vasculature: an intriguing relationship
Hypoxemia is the cardinal symptom in patients with severe coronavirus disease-2019 (COVID-19). However, hypoxemia disproportionate to radiographic opacities has led to growing suspicion that involvement of pulmonary vasculature (PV), leading to shunt physiology, may be a driver of this marked hypoxemia.
The virus’s affinity for PV is explained by presence of angiotensin-converting enzyme 2 receptor, which serves as the functional receptor for SARS-CoV-2, on pulmonary endothelium (. doi: 10.1177/2045894020933088).
This increased affinity predisposes PV to pathologic effects of SARS-CoV-2, noted in COVID-19 patients’ autopsies, which revealed pulmonary endothelial injury and abnormal vessel growth (intussusceptive angiogenesis). These changes, along with profound inflammatory response, further predispose the PV to thrombosis and microangiopathy in COVID-19 ().
These autopsy results also explain the radiologic findings of PV in COVID-19. Dual energy CT scanning, used to evaluate lung perfusion in these patients, has demonstrated PV thickening, mosaicism, and pulmonary vessel dilation; the latter likely occurring due to aberrations in physiologic hypoxic pulmonary vasoconstriction ().
Despite PV’s involvement, only few cases of COVID-19 have been reported in patients with pulmonary arterial hypertension (PAH) , leading to the hypothesis that pre-existing vascular changes may have a protective effect in PAH patients ().
The above discussion details the complex and multifaceted relationship between COVID-19 and PV which underscores the value of understanding this interaction further and may prove to be insightful for discovering potential therapeutic targets in COVID-19.
Humna Abid Memon, MD – Fellow-in-Training Member