The 100 most-cited articles in CHEST Journal, 2023

BACKGROUND: Bone marrow mesenchymal stem cell (BM-MSC)-derived extracellular vesicles (ExoFlo) convey the immunomodulatory and regenerative properties of intact BM-MSCs. This study aimed to determine the safety and efficacy of ExoFlo as treatment for moderate to severe ARDS in patients with severe COVID-19. RESEARCH QUESTION: Do two doses of ExoFlo safely reduce mortality in COVID-19-associated moderate to severe ARDS compared with placebo? STUDY DESIGN AND METHODS: A prospective phase 2 multicenter double-anonymized randomized placebo-controlled dosing trial was conducted at five sites across the United States with infusions of placebo, 10 mL of ExoFlo, or 15 mL of ExoFlo on days 1 and 4. Patients (N = 102) with COVID-19-associated moderate to severe ARDS were enrolled and randomized to treatment. Adverse events were documented throughout the study. The primary outcome measure was all-cause 60-day mortality rate. Secondary outcomes included time to death (overall mortality); the incidence of treatment-emergent serious adverse events; proportion of discharged patients at 7, 30, and…

Background The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal. Research Question How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment? Study Design and Methods The Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined "clinical response" to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required. "Clinical remission" was defined by cessation of exacerbations and maintenance oral corticosteroids, as well as a normalization of lung function (FEV 1 > 80%) and an Asthma Control Questionnaire-6 score ≤ 1.5 following 12 months of treatment. Results Following 12 months of treatment, 104 (21%) of 501 biologic-naive patients had no response to treatment, and 397 (79%) had a clinical response. Among the…

BACKGROUND: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at increased risk of developing the disease. Understanding patients at risk is essential to allow for prompt testing and diagnosis and appropriate management to prevent disease progression. RESEARCH QUESTION: What are the risk factors for NTM-PD that should prompt a physician to consider NTM testing and diagnosis? STUDY DESIGN AND METHODS: Electronic searches of PubMed and EMBASE were conducted in July 2021 for the period 2011-2021. Inclusion criteria were studies of patients with NTM-PD with associated risk factors. Data were extracted and assessed using the Newcastle-Ottawa Scale. Data analysis was conducted using the R-based "meta" package. Only studies that reported association outcomes for cases with NTM-PD compared with control participants (healthy populations or participants without NTM-PD) were considered for the meta-analysis. RESULTS: Of the 9,530 searched publications, 99 met the criteria for the…

Chronic thromboembolic pulmonary hypertension (CTEPH) is a treatable form of pulmonary hypertension and right heart failure. CTEPH (group 4 pulmonary hypertension) is caused by persistent organized thromboembolic obstruction of the pulmonary arteries from incompletely resolved acute pulmonary embolism. CTEPH also may present without prior VTE history, which can contribute to its underrecognition. The true incidence of CTEPH is unclear, but is estimated to be approximately 3% after acute pulmonary embolism. V˙/Q˙ scintigraphy is the best screening test for CTEPH, with CT scan imaging and other advanced imaging methods now playing a larger role in disease detection and confirmation. Perfusion defects on V˙/Q˙ scintigraphy in the setting of pulmonary hypertension are suggestive of CTEPH, but pulmonary angiography and right heart catheterization are required for confirmation and treatment planning. CTEPH potentially is curative with pulmonary thromboendarterectomy surgery, with mortality rates of approximately 2% at expert centers. Advances in operative techniques are allowing more…

Although interstitial lung disease (ILD) is a leading cause of morbidity and mortality in patients with inflammatory myopathies, the current definition and diagnostic criteria of autoimmune myositis remain inadequate to capture the large proportion of patients with lung-dominant disease. As a result, these patients present unique diagnostic and treatment challenges for even the most experienced clinicians. This article highlights the emerging role of autoantibodies in the diagnosis, classification, and management of patients with ILD. We propose alternative nomenclature to facilitate research on this unique patient population. Additionally, evidence supporting the various therapies used in the treatment of myositis-associated ILD is reviewed. The classification and treatment of patients with myositis-associated ILD remains challenging. A standardized therapeutic approach to these patients is lacking, and prospective studies in the field are needed to determine optimal treatment regimens.

BACKGROUND: Standard treatment for early-stage or locoregionally advanced non-small cell lung cancer (NSCLC) includes surgical resection. Recurrence after surgery is commonly reported, but a summary estimate for postsurgical recurrence-free survival (RFS) in patients with NSCLC is lacking. RESEARCH QUESTION: What is the RFS after surgery in patients with stage I-III NSCLC at different time points, and what factors are associated with RFS? STUDY DESIGN AND METHODS: A systematic search was performed in MEDLINE, EMBASE, and Cochrane databases between January 2011 and June 2021. The primary outcome was RFS at 1, 2, 3, and 5 years postresection. Single-arm, random-effects meta-analyses were done to calculate effect estimates and 95% CIs. Analyses were stratified by stage/substage as per the AJCC Cancer Staging Manual, and RFS was estimated (1) after pooling studies, using seventh or eighth edition staging criteria; and (2) among studies using only the eighth edition. Meta-regressions were performed to assess associations between RFS and patient demographic/clinical characteristics of…

Background We previously showed in patients with poorly controlled eosinophilic asthma that a single dose of benralizumab resulted in significantly improved Asthma Control Questionnaire (ACQ-6) score and 129 Xe MRI ventilation defect percent (VDP) 28 days postinjection, and 129 Xe MRI VDP and CT airway mucus occlusions were shown to independently predict this early ACQ-6 response to benralizumab. Research Question Do early VDP responses at 28 days persist, and do FEV 1 , fractional exhaled nitric oxide, and mucus plug score improve during a 2.5 year treatment period? Study Design and Methods Participants with poorly controlled eosinophilic asthma completed spirometry, ACQ-6, and MRI, 28 days, 1 year, and 2.5 years after initiation of treatment with benralizumab; chest CT was acquired at enrollment and 2.5 years later. Results Of 29 participants evaluated at 28 days post-benralizumab, 16 participants returned for follow-up while on therapy at 1 year, and 13 participants were evaluable while on therapy at 2.5 years post-benralizumab initiation. As compared with 28 days…

Background Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments. Even if high blood eosinophil counts seem to be associated with a reduction in exacerbations with treatment targeting IL-5, we lack biomarkers for the prediction of remission after these very expensive treatments. Research Question Are there biomarkers of remission after therapy targeting IL-5 in the sputum of patients with severe eosinophilic asthma? Study Design and Methods This observational study included 52 patients with severe asthma initiated with anti-IL-5 therapy and recruited from the asthma clinic of the Centre Hospitalier Universitaire of Liege, Belgium. Remission was defined as patients who combined the following at 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire score < 1.5, asthma control test score > 19, or both; FEV 1 of ≥ 80% predicted, improvement of FEV 1 of ≥ 10%, or both; and a blood eosinophil count < 300 cells/μL. Eosinophil peroxidase (EPX),…

BACKGROUND: Despite the significant burden posed by COPD to health care systems, there is a lack of up-to-date information quantifying the general COPD burden, costs, and long-term projections to various stakeholders in the United States. RESEARCH QUESTION: What are the updated state-specific and nationwide estimates of the COPD disease burden and direct costs in 2019, along with projections of COPD-attributable medical costs through 2029? STUDY DESIGN AND METHODS: A cross-sectional, retrospective study design using the 2016 to 2019 Medical Expenditure Panel Survey, 2019 American Community Survey, and 2019 Behavioral Risk Factor Surveillance System data was applied to generate COPD-attributable expenditure estimates. Cost projections for the years 2020 to 2029 were based on 2017 national population projections reported by the US Census Bureau, and all costs were adjusted to 2019 US dollars. RESULTS: In total, 4,135 people living with COPD were included; a higher proportion had other concurrent conditions such as cardiovascular-related conditions compared with people without COPD (n…

BACKGROUND: Navigating through the bronchial tree and visualizing all bronchial segments is the initial step toward learning flexible bronchoscopy. A novel bronchial segment identification system based on artificial intelligence (AI) has been developed to help guide trainees toward more effective training. RESEARCH QUESTION: Does feedback from an AI-based automatic bronchial segment identification system improve novice bronchoscopists' end-of-training performance? STUDY DESIGN AND METHODS: The study was conducted as a randomized controlled trial in a standardized simulated setting. Novices without former bronchoscopy experience practiced on a mannequin. The feedback group (n = 10) received feedback from the AI, and the control group (n = 10) trained according to written instructions. Each participant decided when to end training and proceed to performing a full bronchoscopy without any aids. RESULTS: The feedback group performed significantly better on all three outcome measures (median difference, P value): diagnostic completeness (3.5 segments, P < .001), structured progress (13.5…

BACKGROUND: COPD has been found to be associated with frailty. However, longitudinal evidence for associations of COPD with frailty progression is inadequate. Furthermore, recent studies revealed a new phenotype of lung function impairment: preserved ratio impaired spirometry (PRISm) findings. Associations of PRISm findings and their transitions with frailty progression are unclear. RESEARCH QUESTION: What are the associations of PRISm findings, transitions of PRISm findings, and COPD with frailty progression? STUDY DESIGN AND METHODS: To analyze the associations of PRISm findings and COPD with frailty progression, 5,901 patients were included from the English Longitudinal Study of Ageing. Patients were classified into three lung function patterns of normal spirometry (NS) findings, PRISm findings, and COPD. Frailty progression was assessed by repeated measurements of the frailty index (FI) during follow-up. Among these 5,901 patients, 3,765 patients were included to analyze the associations of PRISm findings transitions with frailty progression. PRISm findings transitions were…

BACKGROUND: Patients with COPD are at high risk of lung cancer developing, but no validated predictive biomarkers have been reported to identify these patients. Molecular profiling of exhaled breath by electronic nose (eNose) technology may qualify for early detection of lung cancer in patients with COPD. RESEARCH QUESTION: Can eNose technology be used for prospective detection of early lung cancer in patients with COPD? STUDY DESIGN AND METHODS: BreathCloud is a real-world multicenter prospective follow-up study using diagnostic and monitoring visits in day-to-day clinical care of patients with a standardized diagnosis of asthma, COPD, or lung cancer. Breath profiles were collected at inclusion in duplicate by a metal-oxide semiconductor eNose positioned at the rear end of a pneumotachograph (SpiroNose; Breathomix). All patients with COPD were managed according to standard clinical care, and the incidence of clinically diagnosed lung cancer was prospectively monitored for 2 years. Data analysis involved advanced signal processing, ambient air correction, and statistics based on…

BACKGROUND: Both the incidence of lung cancer and the prevalence of metabolic syndrome (MetS) have been increasing worldwide. The relationship between MetS and lung cancer remains controversial. RESEARCH QUESTION: What is the risk of lung cancer associated with MetS and its components? STUDY DESIGN AND METHODS: Multivariable Cox regression models were used to estimate the hazard ratio (HR) of MetS-related variables on lung cancer risk, both overall and by histologic subtype, in the UK Biobank. Stratified analyses were conducted by sex, tobacco use status, and use of medication. HR curves were used to test the nonlinear associations between the metabolic markers and the risk of lung cancer. RESULTS: Of the 331,877 participants included in this study, a total of 77,173 participants had a diagnosis of MetS at enrollment. During a median follow-up of 10.9 years, lung cancer as the primary site developed in 2,425 participants. The HRs of MetS were 1.21 (95% CI, 1.09-1.33), 1.28 (95% CI, 1.10-1.50), and 1.16 (95% CI, 0.94-1.44) for the overall risk of lung cancer, adenocarcinoma, and…

BACKGROUND: IV fluids are recommended for adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists. RESEARCH QUESTION: Do lower vs higher fluid volumes improve patient-important outcomes in adult patients with sepsis? STUDY DESIGN AND METHODS: We updated a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials assessing lower vs higher IV fluid volumes in adult patients with sepsis. The coprimary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. We followed the recommendations from the Cochrane Handbook and used the Grading of Recommendations Assessment, Development and Evaluation approach. Primary conclusions were based on trials with low risk of bias if available. RESULTS: We included 13 trials (N = 4,006) with four trials (n = 3,385) added to this update. The meta-analysis of all-cause mortality in eight trials with low risk of bias showed a relative risk of 0.99 (97% CI, 0.89-1.10; moderate certainty evidence). Six trials…

BACKGROUND: The implementation of simulation-based training (SBT) to teach flexible bronchoscopy (FB) skills to novice trainees has increased during the last decade. However, it is unknown whether SBT is effective to teach FB to novices and which instructional features contribute to training effectiveness. RESEARCH QUESTION: How effective is FB SBT and which instructional features contribute to training effectiveness? STUDY DESIGN AND METHODS: We searched Embase, PubMed, Scopus, and Web of Science for articles on FB SBT for novice trainees, considering all available literature until November 10, 2022. We assessed methodological quality of included studies using a modified version of the Medical Education Research Study Quality Instrument, evaluated risk of bias with relevant tools depending on study design, assessed instructional features, and intended to correlate instructional features to outcome measures. RESULTS: We identified 14 studies from an initial pool of 544 studies. Eleven studies reported positive effects of FB SBT on most of their outcome measures. However, risk of…

BACKGROUND: OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism. RESEARCH QUESTION: Does OSA in adults associate with the composition and functional potential of the human gut microbiota? STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the…

BACKGROUND: Pulmonary involvement is the leading cause of death in systemic sclerosis (SSc) and may manifest as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), or in combination of both (ILD with pulmonary hypertension [ILD-PH]). The aim of this analysis was to determine prevalence, clinical characteristics, and survival of these different forms within the registry of the German Network for Systemic Sclerosis. RESEARCH QUESTION: Does SSc-associated ILD-PH or ILD without PH affect survival differently, and are there any risk factors that have an additional impact? STUDY DESIGN AND METHODS: Clinical data of 5,831 patients with SSc were collected in the German Network for Systemic Sclerosis registry. Kaplan-Meier estimates were used to compare overall survival in patients with SSc-associated ILD-PH and ILD without PH with patients without pulmonary involvement and those with PAH. The Cox proportional hazard model was used to analyze the influence of pulmonary involvement and other potential predictors on patient survival. RESULTS: Clinical data of 3,257 patients…

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is considered a complication of pulmonary embolism (PE). However, signs of CTEPH may exist in patients with a first symptomatic PE. RESEARCH QUESTION: Which radiologic findings on CT pulmonary angiography (CTPA) at the time of acute PE could indicate the presence of preexisting CTEPH? STUDY DESIGN AND METHODS: This study included unselected patients with acute PE who were prospectively followed up for 2 years with a structured visit schedule. Two expert radiologists independently assessed patients' baseline CTPAs for preexisting CTEPH; in case of disagreement, a decision was reached by a 2:1 majority with a third expert radiologist. In addition, the radiologists checked for predefined individual parameters suggesting chronic PE and pulmonary hypertension. RESULTS: Signs of chronic PE or CTEPH at baseline were identified in 46 of 303 included patients (15%). Intravascular webs, arterial narrowing or retraction, dilated bronchial arteries, and right ventricular hypertrophy were the main drivers of the assessment. Five…

Background Emerging data suggest that determination of physiologic endotypic traits (eg, loop gain) may enable precision medicine in OSA. Research Question Does a single-night assessment of polysomnography-derived endotypic traits provide reliable estimates in moderate to severe OSA? Study Design and Methods Two consecutive in-lab polysomnography tests from a clinical trial (n = 67; male, 69%; mean ± SD age, 61 ± 10 years; apnea-hypopnea index [AHI] 53 ± 22 events/h) were used for the reliability analysis. Endotypic traits, reflecting upper airway collapsibility (ventilation at eupneic drive [V passive ]), upper airway dilator muscle tone (ventilation at the arousal threshold [V active ]), loop gain (stability of ventilatory control, LG1), and arousal threshold (ArTh) were determined. Reliability was expressed as an intraclass correlation coefficient (ICC). Minimal detectable differences (MDDs) were computed to provide an estimate of maximum spontaneous variability. Further assessment across four repeated polysomnography tests was performed in a subcohort (n = 22). Results…

BACKGROUND: Persistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE). Rehabilitation is a potential treatment option, but the scientific evidence is limited. RESEARCH QUESTION: Does an exercise-based rehabilitation program improve exercise capacity in PE survivors with persistent dyspnea? STUDY DESIGN AND METHODS: This randomized controlled trial was conducted at two hospitals. Patients with persistent dyspnea following PE diagnosed 6 to 72 months earlier, without cardiopulmonary comorbidities, were randomized 1:1 to either the rehabilitation or the control group. The rehabilitation program consisted of two weekly sessions of physical exercise for 8 weeks and one educational session. The control group received usual care. The primary end point was the difference in Incremental Shuttle Walk Test between groups at follow-up. Secondary end points included differences in the Endurance Shuttle Walk Test (ESWT), QoL (EQ-5D and Pulmonary Embolism-QoL questionnaires) and dyspnea (Shortness of Breath questionnaire). RESULTS: A…

Background Lymphangioleiomyomatosis is a progressive diffuse cystic lung disease with approximately 85% survival at 10 years. The determinants of disease progression and mortality after the introduction of sirolimus therapy and vascular endothelial growth factor D (VEGF-D) as a biomarker have not been well defined. Research Question Which factors, including VEGF-D and sirolimus therapy, influence disease progression and survival prognosis in patients with lymphangioleiomyomatosis? Study Design and Methods The progression dataset and the survival dataset included 282 and 574 patients, respectively, from Peking Union Medical College Hospital, Beijing, China. A mixed-effects model was used to compute the rate of decline in FEV 1 , and generalized linear models were used to identify variables affecting FEV 1 decline. A Cox proportional hazards model was used to explore the association between clinical variables and the outcomes of death or lung transplantation in patients with lymphangioleiomyomatosis. Results VEGF-D levels and sirolimus treatment were associated with FEV 1 changes and…

BACKGROUND: Monocyte distribution width (MDW) is an emerging biomarker for infection. It is available easily and quickly as part of the CBC count, which is performed routinely on hospital admission. The increasing availability and promising results of MDW as a biomarker in sepsis has prompted an expansion of its use to other infectious diseases. RESEARCH QUESTION: What is the diagnostic performance of MDW across multiple infectious disease outcomes and care settings? STUDY DESIGN AND METHODS: A systematic review of the diagnostic performance of MDW across multiple infectious disease outcomes was conducted by searching PubMed, Embase, Scopus, and Web of Science through February 4, 2022. Meta-analysis was performed for outcomes with three or more reports identified (sepsis and COVID-19). Diagnostic performance measures were calculated for individual studies with pooled estimates created by linear mixed-effects models. RESULTS: We identified 29 studies meeting inclusion criteria. Most examined sepsis (19 studies) and COVID-19 (six studies). Pooled estimates of diagnostic performance…

Background Studies examining agreement between home and clinic spirometry in patients with asthma are limited, with conflicting results. Understanding the strengths and limitations of telehealth and home spirometry is particularly important considering the SARS-CoV-2 pandemic. Research Question How well do home and clinic measurements of trough forced expiratory volume in 1 second (FEV 1 ) agree in patients with uncontrolled asthma? Study Design and Methods This post hoc analysis used trough FEV 1 data from the randomised, double-blind, parallel-group Phase IIIA CAPTAIN (205715; NCT02924688) and Phase IIB (205832; NCT03012061) trials in patients with uncontrolled asthma. CAPTAIN evaluated the impact of adding umeclidinium (UMEC) to fluticasone furoate/vilanterol (FF/VI) via a single inhaler; 205832 investigated adding UMEC to FF versus placebo. Trough FEV 1 measurements were collected via home spirometry and supervised in-person spirometry in the research clinic. To compare home and clinic spirometry, we examined the time-course analyses of home and clinic trough FEV 1 , and…

Background The carbonic anhydrase inhibitor sulthiame reduces OSA severity, increases overnight oxygenation, and improves sleep quality. Insights into how sulthiame modulates OSA pathophysiologic features (endotypic traits) adds to our understanding of the breathing disorder itself, as well as the effects of carbonic anhydrases in respiratory regulation. Research Question How does sulthiame treatment modify endotypic traits in OSA? Study Design and Methods Per-protocol tertiary analysis of a randomized controlled trial with the inclusion criteria as follow: BMI, ≥ 20 to ≤ 35 kg/m 2 ; age, 18-75 years; apnea-hypopnea index (AHI) ≥ 15 events/h; Epworth sleepiness scale score, ≥ 6; as well as nonacceptance or nontolerance of positive airway pressure treatment. Patients were randomized to receive placebo (n = 22), sulthiame 200 mg (n = 12), or sulthiame 400 mg (n = 24) during 4 weeks of treatment. Polysomnography was applied twice, at baseline and follow-up. Endotypic traits were determined from polysomnography tracings (PUPBeta). Sulthiame plasma concentration was analyzed. Differences…

Background Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear. Research Question Do patients hospitalized with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using 1 H and 129 Xe MRI between 6 and 52 weeks following hospitalization? Study Design and Methods Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary 1 H and 129 Xe MRI protocol at 6, 12, 25, and 51 weeks following hospital admission in a prospective cohort study between November 2020 and February 2022. The imaging protocol was as follows: 1 H ultra-short echo time, contrast-enhanced lung perfusion, 129 Xe ventilation, 129 Xe diffusion-weighted, and 129 Xe spectroscopic imaging of gas exchange. Results Nine patients were recruited (age 57 ± 14 [median ± interquartile range] years; six of nine patients were male). Patients underwent MRI at 6 (n = 9), 12 (n = 9), 25 (n = 6), and 51 (n = 8) weeks…

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV infection; however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. RESEARCH QUESTION: What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared with conventional-dose TMP-SMX after adjusting for patient background characteristics? STUDY DESIGN AND METHODS: In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-dose (TMP < 12.5 mg/kg/d) and conventional-dose (TMP 12.5-20 mg/kg/d) groups. The primary end point was 30-day mortality, and the secondary end points were 180-day mortality, adverse events grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates.…

BACKGROUND: One-half of all people who undergo lung cancer screening (LCS) currently use tobacco. However, few published studies have explored how to implement effective tobacco use treatment optimally during the LCS encounter. RESEARCH QUESTION: Was the Optimizing Lung Screening intervention (OaSiS) effective at reducing tobacco use among patients undergoing LCS in community-based radiology facilities? STUDY DESIGN AND METHODS: The OaSiS study (National Cancer Institute [NCI] Protocol No.: WF-20817CD) is an effectiveness-implementation hybrid type II cluster randomized trial of radiology facilities conducted in partnership with the Wake Forest National Cancer Institute Community Oncology Research Program research base. We randomly assigned 26 radiology facilities in 20 states to the intervention or usual care group. Staff at intervention facilities implemented a variety of strategies targeting the clinic and care team. Eligible patient participants were aged 55 to 77 years undergoing LCS and currently using tobacco. Of 1,094 who completed a baseline survey (523 intervention group,…

Background In the phase 3 MANDALA trial, as-needed albuterol-budesonide pressurized metered-dose inhaler significantly reduced severe exacerbation risk vs as-needed albuterol in patients with moderate-to-severe asthma receiving inhaled corticosteroid-containing maintenance therapy. This study (DENALI) was conducted to address the US Food and Drug Administration combination rule, which requires a combination product to demonstrate that each component contributes to its efficacy. Research Question Do both albuterol and budesonide contribute to the efficacy of the albuterol-budesonide combination pressurized metered-dose inhaler in patients with asthma? Study Design and Methods This phase 3 double-blind trial randomized patients aged ≥ 12 years with mild-to-moderate asthma 1:1:1:1:1 to four-times-daily albuterol-budesonide 180/160 μg or 180/80 μg, albuterol 180 μg, budesonide 160 μg, or placebo for 12 weeks. Dual-primary efficacy end points included change from baseline in FEV 1 area under the curve from 0 to 6 h (FEV 1 AUC 0-6h ) over 12 weeks (assessing albuterol effect) and trough…

BACKGROUND: A close relationship exists between OSA and obesity. The impact of obesity on the prognostic significance of OSA in patients with acute coronary syndrome (ACS) remains unclear. RESEARCH QUESTION: Do the effects of OSA on subsequent cardiovascular events in patients with ACS vary with obesity status? STUDY DESIGN AND METHODS: This is a prospective cohort study. Patients 18 to 85 years of age who were hospitalized for ACS were consecutively enrolled and underwent portable sleep monitoring after clinical stabilization. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The primary end point was major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, hospitalization for ACS, stroke, ischemia-driven revascularization, or hospitalization for heart failure. RESULTS: ). During 2.9 years (1.5, 3.6 years) follow-up, the incidence of MACCE was significantly higher in patients with obesity than in patients without obesity (hazard ratio [HR], 1.29; 95% CI, 1.06-1.58; P = .013). Although the prevalence of OSA was lower in patients without…

BACKGROUND: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could impact outcomes negatively, especially for patients who may not derive full treatment benefit from handheld inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that also may be contaminated. This is particularly relevant for patient care in the…

BACKGROUND: In people with OSA, excessive daytime sleepiness is a prominent symptom and can persist despite adherence to CPAP, the first-line therapy for OSA. Pitolisant was effective in reducing daytime sleepiness in two 12-week randomized controlled trials (RCTs), one in patients adherent to CPAP (BF2.649 in Patients With OSA and Treated by CPAP But Still Complaining of EDS [HAROSA 1]) and the other in patients refusing or not tolerating CPAP (BF2.649 in Patients With OSA, Still Complaining of EDS and Refusing to be Treated by CPAP [HAROSA 2]). RESEARCH QUESTION: Does the efficacy and safety of pitolisant persist when these patients take it long-term? STUDY DESIGN AND METHODS: All adults included in the HAROSA 1 and HAROSA 2 RCTs (both pitolisant and placebo arms) were offered pitolisant (up to 20 mg/d) after completion of the short-term double-anonymized phase (ie, from week 13) in an open-label cohort study. The primary efficacy outcome was the change in Epworth Sleepiness Scale score between baseline and week 52. Safety outcomes were treatment-emergent adverse event(s)…

BACKGROUND: The harm associated with imaging abnormalities related to lung cancer screening (LCS) is not well documented, especially outside the clinical trial and academic setting. RESEARCH QUESTION: What is the frequency of invasive procedures and complications associated with a community based LCS program, including procedures for false-positive and benign, but clinically important, incidental findings? STUDY DESIGN AND METHODS: We performed a single-center retrospective study of an LCS program at a nonuniversity teaching hospital from 2016 through 2019 to identify invasive procedures prompted by LCS results, including their indication and complications. RESULTS: Among 2,003 LCS participants, 58 patients (2.9%) received a diagnosis of lung cancer and 71 patients (3.5%) received a diagnosis of any malignancy. Invasive procedures were performed 160 times in 103 participants (5.1%), including 1.7% of those without malignancy. Eight invasive procedures (0.4% of participants), including four surgeries (12% of diagnostic lung resections), were performed for false-positive lung nodules.…

BACKGROUND: Obesity is often associated with uncontrolled, difficult-to-treat asthma and increased morbidity and mortality. Previous studies suggest that weight loss may improve asthma outcomes, but with heterogenous asthma populations studied and unclear consensus on the optimal method of weight management. The Counterweight-Plus Programme (CWP) for weight management is an evidence-based, dietitian-led total diet replacement (TDR) program. RESEARCH QUESTION: Can use of the CWP compared with usual care (UC) improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity? STUDY DESIGN AND METHODS: . The CWP was a 12-week TDR phase (800 kcal/d low-energy formula) followed by stepwise food reintroduction and weight loss maintenance for up to 1 year. The primary outcome was the change in Asthma Control Questionnaire 6 (ACQ6) score over 16 weeks. The secondary outcome was change in Asthma Quality of Life Questionnaire (AQLQ) score. RESULTS: Thirty-five participants were randomized (36 screened) and 33 attended the 16-week follow-up (n = 17 in the CWP…

BACKGROUND: Several characteristics distinguish lung cancer in female patients from that in male patients, with adenocarcinoma being more prevalent in female patients and occurring more frequently in female patients who do not smoke. Uncertainty surrounds the relationship between female-specific reproductive factors and lung cancer risk. RESEARCH QUESTION: Are sex-specific reproductive factors associated with risk of lung cancer in different genetic risk groups and histologic types? STUDY DESIGN AND METHODS: A Cox proportional hazard model was used to evaluate the association between multiple reproductive factors and the risk of lung cancer developing in a prospective cohort study involving 273,190 female individuals from the UK Biobank. Subgroup analyses stratified by age, smoking status, BMI, genetic risk, and histologic subtype were conducted to emphasize the modification effects further. RESULTS: A total of 1,182 cases of lung cancer in female patients were recorded over a median follow-up period of 12.0 years in the cohort study. In multivariable-adjusted models, early menarche…