Thank you for tuning in to the Editor’s Highlight Podcast for the July 2025 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, long-term real-world data on clinical remission in patients with severe eosinophilic asthma (SEA) receiving biologics are lacking. In this issue, Pelaia and colleagues report findings from a multinational, retrospective, real-world program that included 1,070 adults with SEA who received benralizumab. The study was designed to determine if long-term clinical remission is a viable goal for patients with SEA receiving benralizumab. Of the patients, 39% and 31% met the three-component clinical remission criteria at 48 and 96 weeks, respectively. Of biologic-naïve individuals, 43% achieved remission (compared with 32% in those who were biologic-experienced). A lower mean oral corticosteroid dose (OR, 0.51), lower BMI (OR, 0.56), and higher peak eosinophil count (OR, 1.68) were associated with achieving clinical remission. These findings suggest that clinical remission is a realistic goal when treating patients with SEA and suggest further research about earlier initiation of biologic therapy is warranted.
Next is our Chest Infections content area. Recent studies have quantified “uncertainty zones” of interferon-gamma release assays (IGRAs). It is unclear how this will impact a determination of the frequency of clearance of Mycobacterium tuberculosis infection. In this issue, Chen and colleagues report findings from five cohorts, including 7,683 participants who had three or more IGRAs, in order to determine the trajectories of IGRA results over two years of testing when accounting for uncertainty zones with stringent cutoffs. Stringent reversion at year two following conversion at year one varied from 17% to 48% in the different cohorts. In the US cohort, reversion at year one following conversion at six months was 58% for QuantiFERON and 18% for T-SPOT.TB. In one cohort from China, IGRA reversion was more common in younger participants and those without recent close TB exposure. These findings suggest high annual rates of IGRA reversion despite application of the uncertainty zone.
Our COPD content area is next. Patient-reported outcomes are important considerations when determining appropriate COPD therapy. In this issue, Bhatt and colleagues report findings from two phase 3 trials, including 1,660 patients with COPD and type 2 inflammation receiving triple therapy who were randomized to receive dupilumab or placebo. The study was conducted to determine if add-on dupilumab treatment improves health-related quality of life and respiratory symptoms in patients with COPD and type 2 inflammation. At week 52, dupilumab treatment reduced St. George’s Respiratory questionnaire (SGRQ) and Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total scores; the SGRQ domain-specific scores for symptoms, activity, and impacts; and the E-RS:COPD domain scores of breathlessness, cough and sputum, and chest symptoms. These findings highlight improvements in patient-reported outcomes in patients with COPD and type 2 inflammation treated with dupilumab. Other original research appearing in this section includes a study characterizing occupational endotoxin-related small airways disease with paired inspiratory/expiratory CT scans; a systematic review and meta-analysis of the prevalence of airflow limitation and emphysema in lung cancer screening populations; and an evaluation of preserved ratio impaired spirometry as a risk factor for developing COPD in those who haven’t smoked. Completing this section is a CHEST Review on growing up with developmental lung diseases.
Next is our Critical Care content area. The cuff leak test (CLT) is an important tool to assess the risk of upper airway obstruction after extubation. In this issue, Tang and colleagues present findings from a prospective, multicenter, randomized controlled trial of 536 subjects, designed to assess whether a modified CLT approach (including a semirecumbent position, lower inspiratory flow rate, set breathing frequency, and positive end-expiratory pressure of 0) has superior ability to predict reintubation than the traditional method. The incidence of reintubation within 48 hours after extubation did not differ between the groups. Postextubation stridor within 24 hours after extubation was more frequent in the modified CLT group (5.22% vs 1.49%), while the invasive mechanical ventilation duration was shorter in the modified CLT group (137 h vs 159 h). These findings suggest the modified CLT may better predict postextubation stridor at 24 hours, but it does not help decrease the reintubation incidence. Also in this section is an original research study evaluating the six-month mortality, care pathways, and quality of life in critically ill patients with prolonged mechanical ventilation and a research letter that evaluates the use of high-dose hydroxocobalamin for septic shock. Completing this section is a Special Features article that describes vascular disturbances of the skin in critically ill patients.
On to our Diffuse Lung Disease content area. The role of 2-Deoxy-2-[18F]fluoro-d-glucose (FDG)-PET imaging in predicting treatment response and guiding therapy outside of cardiac disease is not completely understood. In this issue, Donnelly and colleagues present findings from a survey of 215 physicians about the perceived utility of FDG-PET imaging in the diagnosis and treatment decisions of a series of cases. Pulmonary sarcoidosis case vignettes had the lowest rates of FDG-PET endorsement (38%-64%) with near-chance interrater agreement on treatment rationale in the pulmonary and multisystem sarcoidosis cases. Agreement was highest for the cases of cardiac sarcoidosis. These findings suggest a low agreement between physicians regarding the utility of FDG-PET imaging in the management of pulmonary sarcoidosis. Completing this section is an original research study that evaluated the association of interstitial lung abnormalities and preserved ratio impaired spirometry with mortality and a research letter that describes Hermansky-Pudlak syndrome in the United States.
Next is our Education and Clinical Practice content area. There isn’t a unified diagnostic approach for persistent tachypnea of infancy (PTI) or neuroendocrine cell hyperplasia of infancy (NEHI). In this issue, Marczak and colleagues report findings from a European multicenter, retrospective, observational study of 378 children from 17 countries, designed to determine whether the clinical presentation and diagnostic approach are different in patients with PTI or NEHI among the European countries. The most common symptoms and signs were tachypnea, chest retractions, crackles on auscultation, hypoxemia, and failure to thrive. A high-resolution CT (HRCT) scan was performed in all patients and lung biopsy in 23.5%. Histopathologic examination showed a hyperplasia of pulmonary neuroendocrine cells in 52.8%. Genetic testing was uncommon. These findings suggest the diagnosis of PTI or NEHI relies on clinical symptoms and HRCT imaging and highlight a need for guidelines to make the diagnostic approach more uniform. Completing this section is an original research study that estimates the causal effect of double-blind peer review for our journal and a How I Do It review of improving a rapid response system with a performance self-evaluation tool.
Our Pulmonary Vascular content area is next. Treatment targeting the right ventricle in pulmonary arterial hypertension (PAH) does not exist. In this issue, Leary and colleagues present findings from a 24-week, single-center, 1:1 randomized, double-masked, placebo-controlled trial of the H2-receptor antagonist famotidine in 80 patients with a diagnosis of PAH. No significant difference in the primary outcome of 6-minute walk distance at 24 weeks was found. There were also no differences in secondary end points at 24 weeks. These results do not support the routine use of famotidine as an adjunct therapy for the treatment of PAH. Completing this section is an original research study that evaluated the association and minimally important differences of physical activity measured by hip-anchored accelerometry in pediatric pulmonary hypertension with disease severity.
Next is our Sleep Medicine content area. Pimavanserin, a promising serotonin 2A receptor antagonist, may help to counteract the wake-promoting properties of the noradrenergic muscle stimulant atomoxetine by increasing the arousal threshold and possibly reducing OSA severity. In this issue, Messineo and colleagues report findings from a randomized, crossover, two-period, double-blind clinical trial of 18 participants with OSA, designed to determine the effect of the combination of pimavanserin and atomoxetine on the apnea-hypopnea index (AHI), arousal index, and nadir oxygen saturation (SpO2). Combination therapy reduced the AHI by 42% with an absolute AHI reduction of 16.9 events/hour compared with placebo. The nadir SpO2 and arousal index were also improved, while the overnight heart rate was increased. Treatment improved pharyngeal collapsibility, reduced loop gain, and did not reduce the arousal threshold. These findings suggest the combination of pimavanserin with atomoxetine is a candidate for OSA therapy.
Next is our Thoracic Oncology content area. The optimal strategy for selecting biopsy devices during electromagnetic navigation bronchoscopy (ENB) is unclear. In this issue, Kim and colleagues report findings from a randomized crossover study of 142 participants undergoing ENB under moderate sedation for peripheral pulmonary lesions that randomized the order of needle aspiration and forceps biopsy to determine if the combination of the biopsy types improves diagnostic yield compared with that of a single device alone. The diagnostic yield was 44.4% for forceps biopsy, 51.4% for needle aspiration, and 66.9% for the combination. The sensitivity for malignancy also improved with the combination of biopsy modalities. Pneumothorax occurred in 3.5% of patients, with 1.4% requiring tube drainage. These findings suggest that a multimodal approach that uses both needle biopsy and forceps biopsy is a valid diagnostic strategy. Also in this section is a systematic review of interventions to improve adherence to clinical guidelines for the management and follow-up of pulmonary nodules and a Special Features article on missed opportunities for lung cancer screening among behavioral health patients with elevated cigarette smoking rates.
I encourage you to read our Commentary series, where you will find an update on cardiopulmonary imaging with 0.55T MRI. Finally, please review our case series publications for the month, which 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 July issue.