Thank you for tuning in to the Editor’s Highlight Podcast for the May 2022 issue of the journal CHEST®. There is a great lineup of diverse content in this month’s issue.
Over the next 15 minutes, I will provide a brief overview of key manuscripts published in each of our content areas.
Starting with our Asthma content area, evidence suggests that people with characteristics of both asthma and COPD experience worse outcomes than those with either condition. In this issue, John and colleagues conducted a genome-wide association study of 8,068 case subjects with asthma-COPD overlap and 40,360 control subjects without asthma or COPD to determine the genetic architecture of asthma-COPD overlap and assess whether the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma. Thirty-one independent variants were selected for further investigation, and eight novel signals were detected. The signals suggested a spectrum of shared genetic influences, some influencing asthma and others fixed airflow obstruction. The associations of these signals were not driven by smoking or age. Eosinophil counts, atopy, and asthma traits were prominent in phenome scans. These signals of asthma-COPD overlap may represent loci that predispose to type 2 inflammation and serious long-term consequences of asthma.
Next is our Chest Infections content area. It is uncertain whether primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is helpful in those being treated with rituximab. In this issue, Park and colleagues report the results of a retrospective study of 3,524 patients designed to determine if the benefit of primary prophylaxis for PJP in patients receiving rituximab outweighs the potential risk of prophylaxis. During the first 28 days after the start of rituximab, 1,001 patients received TMP-SMX. Ninety-two PJP infections occurred, with a mortality rate of 27.2%. The prophylaxis group had a lower incidence of PJP (heart rate 0.20; only one patient). There were 10 severe adverse drug reactions amounting to a number needed to harm of 101 and a number needed to prevent one PJP infection of 32. These results suggest TMP-SMX prophylaxis significantly reduced PJP incidence with a tolerable safety profile in patients receiving rituximab treatment. Also in this section are original research articles describing real-world outcomes in cystic fibrosis clinical care during the global pandemic, the potential value of sputum proteomics in nontuberculous mycobacterial lung disease, and the impact of time between diagnosis and treatment for nontuberculous mycobacterial disease on culture conversion and all-cause mortality. Completing this section is a CHEST Review describing emerging nonpulmonary complications for adults with cystic fibrosis.
On to our COPD content area. New predictive biomarkers and novel therapeutic targets for COPD will be facilitated by an improved understanding of airway pathophysiology. In this issue, Esther and colleagues evaluated metabolomics biomarkers in the sputa of patients with COPD to determine which physiologic pathways are altered in the airways and can predict exacerbations in people with COPD. Sputum from 562 patients with COPD, 341 individuals who smoke with preserved spirometry, and 77 healthy individuals who have not smoked were analyzed. Biomarkers from multiple pathways were elevated. Sialic acid and hypoxanthine were associated strongly with measures of disease severity and shorter time to exacerbation, improving prediction models of future exacerbations. Pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress were implicated in the pathophysiology of COPD, providing potential targets for therapy and predictors of exacerbations. Also in this section is an original research article exploring the association between disability and mortality with the co-occurrence of physical frailty and COPD and a CHEST Review about the role of palliative care in COPD.
Next is our Critical Care content area. Platelets play an important role in the pathophysiology of ARDS. Prior observational work suggests aspirin is a potential therapeutic option. In this issue, Toner and colleagues report the results of a randomized, double-blind, allocation-concealed, placebo-controlled phase 2 trial, conducted to determine if enteral aspirin at 75 mg once daily is safe and effective in improving surrogate outcomes in adults with ARDS. The trial was stopped after 49 of a planned 60 patients were recruited. There was no significant difference in day 7 oxygenation index or other respiratory physiological markers. There was no difference in the number of adverse events between the groups. These results suggest that though aspirin is well tolerated, it did not improve the oxygenation index or other physiological outcomes, lowering the priority and feasibility of larger studies with similar designs. Also in this section is an original research article that evaluated drivers of burnout among critical care practitioners in a multicenter mixed methods study and a research letter reporting variability in surrogate-informed consent rates in ARDS and PETAL network multicenter trials. Completing this section is a CHEST Review of benign hematology emergencies in critically ill adults and a Special Feature article exploring how adult ICUs can support pediatric care in public health emergencies.
On to our Diffuse Lung Disease content area. The assessment of mortality risk in interstitial lung disease (ILD) remains challenging. In this issue, Comes and colleagues report the results of a multicenter, retrospective, observational cohort study designed to determine if BMI and weight loss over time were reliable prognostic indicators in patients with fibrotic ILD. Derivation and validation cohorts built from six centers each included nearly 1,800 patients. Compared with normal BMI, mortality was highest in those who were underweight and lowest in those who were overweight or obese. Patients with weight loss of at least 2 kg within 1 year had increased risk of death in the subsequent year. These results identify both BMI and weight loss as potentially clinically useful prognostic indicators in fibrotic ILD. A second original research article published in this issue evaluated early radiographic progression of scleroderma lung disease as a predictor of long-term mortality.
Our Education and Clinical Practice content area is next. Chronic mountain sickness (CMS) is characterized by severe hypoxemia and excessive erythrocytosis (EE). Whether the duration of CMS or ageing promotes EE and CMS remains unclear. In this issue, Hamard and colleagues report the results of a longitudinal study designed to prospectively investigate EE, CMS symptoms, and changes in physiologic variables in dwellers from the highest city in the world. Among 90 highlanders followed, the prevalence of EE was 76% and of CMS was 31%. The crude incidence rate over 14 years of follow-up in those without baseline disease was 6.2 and 4.4 cases per person-years respectively. SpO2, CMS clinical score, and years of follow-up were associated with an increase in hematocrit and SpO2, and years of follow-up were associated with an increase in the CMS total score. These results provide insight into the association between chronic severe hypoxic exposure and the occurrence of EE and CMS. Completing this section is a CHEST Review describing clinical and billing aspects of transvenous phrenic nerve stimulation for central sleep apnea.
Next is our Pulmonary Vascular content area. A better understanding of the relationship between indexes of right ventricular function and prognosis in pulmonary hypertension could impact risk stratification. In this issue, Haddad and colleagues report findings from a cohort of 231 patients with pulmonary arterial hypertension (PAH) followed over 7 years to determine if clinical network graphs inform risk stratification in PAH. A network of closely intertwined features centered around NT-proBNP was identified. A prognostic model with a C-index of 0.81 included central right heart features, NT-proBNP, and right ventricular end-systolic remodeling index, with 6 MWD and less connected nodes. Serial change in NT-proBNP improved outcome prediction. These results identified NT-proBNP as a central prognostic factor and connectivity analysis as a tool for feature selection and combination in outcome models. Completing this section is a CHEST Review about the off-label use and inappropriate dosing of direct oral anticoagulants in cardiopulmonary disease.
Our Sleep Medicine content area is next. OSA is associated with metabolic syndrome, but it is not clear if treatment with CPAP can improve the metabolic syndrome. In this issue, Giampa and colleagues report on a randomized, placebo-controlled trial of adult patients with a recent diagnosis of metabolic syndrome and moderate or severe sleep apnea designed to determine if OSA treatment with 6 months of CPAP has effects on the reversibility of metabolic syndrome, including the associated metabolic adiposity and vascular features. One hundred patients completed the study. Though most of those treated with CPAP continued to have metabolic syndrome, the rate of reversibility was higher than in the placebo group: 18% vs 4%. CPAP did not promote significant reductions in many of the individual components of metabolic syndrome but did lead to a very modest reduction in visceral fat and improved endothelial function. These results support a modest role of OSA and OSA treatment in modulating metabolic syndrome.
Next is our Thoracic Oncology content area. Long-term survival according to clinical nodal stage diagnosed by EBUS-TBNA has not been reported. In this issue, Hwangbo and colleagues report the results of a retrospective review of 1,089 patients who underwent EBUS-TBNA for initial lung cancer staging to determine the prognostic impact of EBUS nodal stage and the survival rate in false-negative EBUS-TBNA cases. A significant difference in survival between EBUS nodal stages was observed. Among 55 false-negative cases, patients with pN2-3 disease had worse survival than patients with pN0 but not pN1. These results support the importance of EBUS-TBNA in non-small cell lung cancer staging and suggest a favorable survival in those with false-negative results, providing a rationale for performing surgery after a negative EBUS-TBNA. Also in this section is an original research article reporting results of a dual-institution, multireader study of definitions of central tumors in radiologically node-negative, early-stage lung cancer and a research letter describing the impact of alternative approaches to diagnostic yield calculation in studies of bronchoscopy. Completing this section is a CHEST Review of the frequency, risk factors, and management of complications from pleural procedures.
Finally, I encourage you to take a look at our Humanities in Chest Medicine section, where you will find a Point/Counterpoint debate about whether informed consent should be obtained for apnea testing in the determination of death by neurological criteria and a Vantage series contribution about equity challenges for artificial intelligence algorithms in health care.
Our case series publications for the month provide novel and educational cases to help improve your clinical skills.
I hope you enjoy reading all of the high-quality content available in this month’s issue of the journal CHEST. As always, I am grateful to the authors of this work, to the reviewers who volunteered their time to improve the quality of these manuscripts, and to our editorial board for guiding everything that we do. Until next month, I hope you enjoy the May issue.