FeNO guidelines and the art of clinical medicine
The American Thoracic Society (ATS) recently published new guidelines on the use of fractional exhaled nitric oxide (FeNO) in the management of asthma (Khatri S. Am J). The previous iteration dealt with questions about the interpretation of FeNO levels. However, the updated guidelines address a single question: Should patients with asthma in whom treatment is being contemplated undergo FeNO testing?
Several roles of nitric oxide (NO) have been discovered, including as a marker of eosinophilic airway inflammation or T2-inflammation. The fraction of NO during steady-state exhalation, easily measured by a handheld device, is a standardized quantitative noninvasive method to assess severity of airway eosinophilic inflammation. However, factors like concomitant sinusitis, bronchoconstriction, obesity, and smoking can also affect FeNO levels, and interpretation is context-dependent. Moreover, some biologic agents have variable effects on FeNO while still being effective in controlling T2 inflammation. Therefore, FeNO is neither the broadest nor the most sensitive signal of T2 inflammation, and there is much unknown about using FeNO to guide asthma treatment. Heterogeneity is one of the many challenges, as different endotypes and clinical subsets vary in the inflammatory pathways leading to airway hyperresponsiveness and remodeling.
The panel assessed the value of FeNO testing in improving asthma control questionnaire scores (ACT, ACQ-7), oral corticosteroid use, asthma exacerbations, lung function, health care utilization, and cost-effectiveness. FeNO-guided therapy compared with therapy without FeNO reduced exacerbations and oral corticosteroid use, though effect size was modest. Among other outcomes, while the trend favored FeNO, it did not reach statistical significance. Adverse effects of FeNO testing were trivial, and the cost is moderate though dependent on the institution size and testing frequency. Thus, for clinicians who manage adults and children 4 years of age and older, in whom treatment for asthma is being considered, it is suggested that FeNO testing be done in addition to usual care. The guidelines do not recommend specific steps to modify treatment based on FeNO results but suggest a decision framework, reminding us that clinical context is key and FeNO is merely one signal. In recognizing its own fallibility, this document suggests that in the continually evolving world of asthma, the art of clinical medicine still reigns supreme.
Uddalak Majumdar, MDDr. Majumdar is a Fellow, Pulmonary & Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
Marijuana use in pregnancy
Marijuana is the most commonly used illegal drug in the United States. According to the CDC, about 1 in 20 women report using marijuana while pregnant (). As states legalize marijuana for medicinal or recreational purposes, its use by pregnant women could increase even further. While some use it to ease morning sickness and anxiety, they may not be aware that it can pose risks.
Research has been raising concerns about the effects of marijuana use during pregnancy for years. A study from 1978 linked maternal cannabis use with children’s behavioral problems and deficits in language comprehension, visual perception, attention, and memory (). ). More recent research has linked use to low birth weight, reduced IQ, autism, delusional thoughts, and attention problems, although some other studies have not identified such associations.
A new study shows that children of women who use marijuana during or soon after pregnancy were twice as likely to become anxious, aggressive, or hyperactive. This corresponded with widespread reductions in immune-related gene expression in the placenta, which correlated with anxiety and hyperactivity ().
Chemicals from marijuana can be passed to the baby through breast milk. THC is stored in body fat and slowly released over time. Exposure could still occur even after stopping use (. ACOG Committee Opinion, Number 722, October 2017).
Studies have shown that THC can pass through the mother’s bloodstream to the placenta and the fetus. This occurs independent of how cannabis is consumed (smoking, vaping, eating, or oils/creams). Patients should be educated that no amount has been proven safe to use during pregnancy or breastfeeding.
Anita Rajagopal, MD, FCCP, Respiratory-Related Sleep Disorders Section, Member-at-Large
Dr. Rajagopal is Network Medical Director, Community Physician Network, Sleep Medicine/Medical Director, Community Health Network Sleep-Wake Disorders Center, Community Health Network, Indianapolis, Indiana.