BACKGROUND:Days alive and out of hospital (DAOH) is a validated patient-centered outcome that remains unexplored in lung transplantation (LT). It assesses the proportion of days a patient spends alive and outside of hospital. Quantifying DAOH trajectories around LT could provide patients with realistic expectations and better prepare them for the demanding post-transplant period. MATERIALS AND METHODS:DAOH was calculated for the year before (DAOH-BF) and two years after first LT (DAOH-AF1, DAOH-AF2) for all patients transplanted in France between 2020 and 2023. Clinical variables were collected to identify predictors of DAOH-AF1 using a two-part model. RESULTS:1,222 patients were included (56% male; median age 57, IQR 47-62). Median DAOH-BF was 95% (IQR, 89-99%), whereas median DAOH-AF1 declined to 80% (IQR, 64-87%, p < 0.001). Among patients discharged after the transplantation-related hospital stay, connective tissue disease (β = -4.1, p = 0.05) and single-LT (β = -4.0, p = 0.040) were independently associated with lower DAOH-AF1. Median DAOH-AF2 subsequently recovered to 98.6% (IQR, 95.1-100%). CONCLUSION:DAOH is significantly reduced during the first post-LT year, particularly among patients with connective tissue disease and in case of single LT. These findings have direct implications for pre-LT counselling, informing patients about the demanding nature of the first year post-LT while offering reassurance that DAOH improves substantially beyond this period. Identified predictors of lower DAOH-AF1 allow clinicians to further tailor pre-LT information to high-risk subgroups.
Background Expiratory pressure alleviation (EPA) algorithms have been incorporated into CPAP devices to reduce expiratory discomfort during treatment of obstructive sleep apnea (OSA). Since pharyngeal narrowing or collapse can occur during expiration, EPA may impair upper airway patency. Research Question Does EPA compromise upper airway patency and CPAP efficacy in patients with severe OSA? Study Design and Methods Adults with severe OSA using nasal CPAP were considered to participate. The study was conducted in four steps. Steps 1 and 2 were performed during a single overnight polysomnography (PSG) study. In step 1, peak inspiratory flow (PIF) was measured during inspiratory flow limitation with and without EPA. In step 2, CPAP titration was performed in randomized order with and without EPA. Steps 3 and 4 were conducted at home. Residual AHI and adherence were compared with and without EPA activation during fixed (Step 3) and auto-CPAP (Step 4). Results Twenty-nine subjects were studied (55% female; age 63±12 years; BMI 37±7 kg/m2; AHI 58 (39-83) events/h). EPA activation reduced PIF compared to without EPA (0.38 (0.34-0.42) vs 0.19 (0.15-0.23) L/s), respectively (P<0.001). Manually titrated CPAP level was higher with EPA than without EPA (11.40 ± 1.95 vs 9.17 ± 1.78 cmH2O), respectively (P<0.001). Residual AHI was higher with EPA than without EPA, during fixed (3.7 ± 2.2 vs 1.3 ± 0.6 events/h) and automatic CPAP (1.4 (0.6 - 2.1) vs (0.8 (0.5-1.8) events/h), respectively (P<0.05). No significant change in CPAP adherence was observed, during fixed (7.0 ± 0.8 vs 7.2 ± 1.0 hours) and automatic CPAP (7.0 ± 1.3 vs 6.9 ± 1.3 hours), with (P=0.497) and without (P=0.506) EPA, respectively. Interpretation EPA application compromised upper airway patency and required higher therapeutic CPAP than without EPA. EPA also impaired OSA control but did not impact CPAP adherence. Clinical Trials Registry NCT05219591.
Palliative care (PC) is defined as a holistic, multidisciplinary, person-centered approach aimed at relieving symptoms and improving quality of life (QoL) for individuals with serious health-related disease. Although recommended by major respiratory societies, patients with advanced chronic respiratory diseases (CRD) continue to have insufficient access to PC, often limited to end-of-life (EoL) care. Compared with patients with lung cancer, patients with CRD experience greater symptom burden, are less informed about their illness, and are less involved in decision-making. Early PC has been shown to improve QoL, reduce depression, decrease avoidable hospitalizations, and support better EoL trajectories.To improve PC providing for patients living with CRD, an interdisciplinary, nurse-led, outpatient PC consultation model was developed and iteratively refined guided by the Plan-Do-Study-Act cycle, as an implementation framework. Patients are referred to the consultation based on symptom burden, decline in respiratory status, frailty, need for discussion on treatment choice, or caregiver strain. During the initial consultation, a PC physician and nurse explore patient and caregiver perceptions of PC, provide information about the aim of this service, and conduct a comprehensive symptom assessment. Follow-up is primarily coordinated by the specialist PC nurse, who ensures symptom evaluation, care coordination, and knowledge on pharmacological and non-pharmacological interventions. Integrative therapies such as hypnosis, reflexology, and Touch-Massage® are also offered, along with discussions around advance care planning when desired.Early, needs-based PC can be effectively integrated into CRD trajectories when delivered through a nurse-led interdisciplinary model of coordination.
Background Cigarette smoking remains the leading cause of preventable death in the United States, with high prevalence among hospitalized patients. Hospitalization presents an opportunity to initiate and engage patients in tobacco treatment, yet guidance for tobacco treatment in this setting has been limited. This clinical practice guideline provides evidence-based recommendations for tobacco treatment in the inpatient setting. Study Design and Methods A multidisciplinary panel followed CHEST’s standardized clinical practice guideline methodology, including systematic literature searches in MEDLINE, Embase, and the Cochrane Database. Key clinical questions were framed using the PICO format. Eligible studies included randomized controlled trials and cohort studies. Evidence was appraised using GRADE, and recommendations were formulated through a modified Delphi process to achieve consensus. Results We identified 9330 abstracts, assessed 252 full texts, and included 142 studies. The literature review and analysis, based on 6 PICO questions, yielded 8 recommendations. No recommendations were supported by high-certainty evidence specific to inpatient tobacco treatment settings. Of the eight recommendations, four were supported by moderate-certainty evidence, two by low-certainty evidence, and two by very low-certainty evidence, supplemented by expert consensus. Interpretation Hospitalization offers a critical window to initiate tobacco treatment. This guideline synthesizes the existing literature to inform key components of inpatient tobacco treatment, including an opt-out population-based approach that proactively provides counseling and pharmacotherapy to all patients who smoke unless they explicitly decline; the initiation and selection of pharmacotherapies during hospitalization; counseling approaches delivered during the inpatient stay; and post-discharge counseling approaches following hospital discharge. Implementing these approaches is likely to improve smoking-cessation outcomes and reduce hospital readmissions and costs. The guideline also evaluates the strength and limitations of the current evidence base and identifies priority areas for future research, including identifying optimal implementation strategies, equity considerations, and the evaluation of cost-effectiveness across diverse hospital settings and patient populations.
Topic importance Asthma is a heterogenous airways disease characterized by variable airflow limitation, airway inflammation and bronchial hyperresponsiveness. There is evidence to suggest that the airway microbiome plays an important role in asthma pathophysiology. Most microbiome studies have investigated the bacterial constituents of the microbiome and further studies are needed to investigate the role of the airway virome and mycobiome in asthma. Review findings Airway microbiome dysbiosis is associated with asthma development, disease severity and inflammatory endotypes. However, it remains unclear whether dysbiosis drives inflammation or is a result of inflammation. Haemophilus and Moraxella alongside rhinovirus and respiratory syncytial virus have been shown to be associated with the development of asthma in children. In established asthma, airway microbiome dysbiosis is associated with severity and risk of exacerbation. Distinct airway microbiome profiles are observed for the different inflammatory endotypes. Asthmatic patients with eosinophilic inflammation have higher microbial diversity similar to healthy individuals while neutrophilic inflammation is associated with reduced microbial diversity, higher bacterial load and a pathogen-dominated microbiome profile suggesting an important role for dysbiosis in asthma that is currently refractory to anti-T2 biologic therapy. Summary To understand the role of the microbiome in asthma, microbiome data must be integrated with other ‘omic approaches’ such as proteomics. Recent studies have used a multi-omic approach to investigate the microbiome and host interaction as well as identifying asthma endotypes and potential therapeutic targets. Antibiotics, probiotics, monoclonal antibodies, and diet could theoretically be used to therapeutically target the airway and gut microbiome in asthma.
BACKGROUND:The Venous Excess Ultrasound (VExUS) score is increasingly used to assess systemic venous congestion, yet direct validation against invasively measured right atrial pressure (RAP) in pulmonary hypertension (PH) remains limited. RESEARCH QUESTION:How accurate is the VExUS score to predict RAP in patients with established or suspected PH? METHODS:We conducted a multicenter observational study across 7 Italian reference centers including patients referred for PH and undergoing a VExUS assessment and right heart catheterization within 1 hour. A VExUS score was calculated with a 0 to 3 grading based on inferior vena cava (IVC) diameter and collapsibility, and Doppler assessment of hepatic, portal, and intrarenal venous flow patterns. The diagnostic performance of VExUS for identifying elevated RAP thresholds was compared with echocardiographic estimates based on IVC diameter and inspiratory collapse and RA surface areas using a multivariable analysis followed by receiver operator curves (ROC) calculations. Subgroup analyses were performed across pulmonary hemodynamic phenotypes (normal hemodynamics vs pre- vs postcapillary PH). RESULTS:The study included 145 patients with pre-capillary PH, most of whom with pulmonary arterial hypertension (PAH), 21 with post-capillary PH, and 21 with no PH. The VExUS score showed a strong graded association with RAP, with mean RAP increasing across VExUS grades (0: 3.9 mmHg; 1: 8.4 mmHg; 2: 13.5 mmHg; 3: 15.8 mmHg; p<0.001). The VExUS score demonstrated excellent discrimination for elevated RAP >12 mmHg (AUC 0.97, 95% CI 0.94-0.99), with higher diagnostic performance than isolated echocardiographic markers and performance comparable to echocardiographic RAP estimation. These findings were consistent across hemodynamic phenotypes.
Background Septic shock is a major cause of intensive care unit (ICU) admission among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, yet data on its epidemiology and prognosis remain limited. Research Question We aimed to describe outcomes, identify independent prognostic factors, and explore associations that may inform early management. Study Design and Methods We performed a multicenter retrospective cohort study including allo-HSCT recipients admitted to the ICU with septic shock between 2015 and 2020. Results Among 1,164 allo-HSCT recipients hospitalized in ICU, 38% (n=444) were admitted for septic shock. The median SOFA score was 8 (IQR, 6-11). Microbiological documentation was obtained in 62% (n=261), including fungal pathogens in 17% (n=74). The respiratory tract was the most common infection source (43%, n=180). Invasive mechanical ventilation and renal replacement therapy were required in 64% (n=284) and 32% (n=143), respectively. Mortality at 90 days and 3 years was 63% (n=280) and 81% (n=350).In the extended Cox model, fungal documentation (HR 1.78 [95% CI, 1.19-2.67], p=0.005), SOFA score (HR 1.07 [95% CI, 1.02-1.13], p=0.007), and neutropenia (HR 3.94 [95% CI, 1.18-13.1], p=0.026) were independently associated with 90-day survival. In a 48-hour landmark analysis, early aminoglycoside use was associated with higher 90-day survival (HR 0.46 [95% CI, 0.33-0.64], p<0.001). However, time-varying analyses indicated a non-constant association over time. Age ≥ 56 years (HR 1.36, [95% CI, 0.99-1.87]), GvHD type, and early bacterial documentation (HR 0.90, [95% CI, 0.64-1.26]) were not associated with 90-day survival. Interpretation Septic shock after allo-HSCT carries a high mortality (63% at 90 days), largely driven by host-related factors and initial illness severity. The association between aminoglycoside use and outcome is complex, does not support a straightforward causal interpretation, and warrants further prospective evaluation.
Background Cough is common in idiopathic pulmonary fibrosis (IPF) and substantially impairs quality of life, but effective treatment options are limited. Gabapentin reduces cough in refractory chronic cough, but its efficacy and safety in IPF-related cough are uncertain. Research Question Does gabapentin improve cough in patients with IPF? Study Design and Methods This study was a randomized, double-blind, placebo-controlled clinical trial conducted at Tongji Hospital, Tongji University. Patients diagnosed with IPF according to the ATS/ERS/JRS/ALAT guidelines, with chronic cough lasting for more than 8 weeks and a cough visual analog scale (VAS) score ≥40 mm, were included. Participants were randomly assigned in a 1:1 ratio to receive either gabapentin or placebo. Gabapentin was titrated to a maximum of 900 mg/d during 12 weeks of treatment, followed by a 4-week post-treatment follow-up. The primary endpoint was the cough relief rate at T4 (end of treatment), defined as the proportion of participants achieving a reduction of at least 50% in total Cough Symptom Score (CSS) from baseline. Safety was assessed in all participants who received at least one dose of study treatment. Results Between May 1, 2021, and December 31, 2024, 72 participants were screened, of whom 68 were randomized to gabapentin or placebo. Five participants withdrew prior to study completion. At T4, the cough relief rate was higher with gabapentin than with placebo (73.5% vs 26.5%), with a placebo-adjusted absolute difference of 47.1 percentage points (95% CI, 26.1-68.0; P < 0.001). During treatment, adverse events occurred in 32.4% of participants receiving gabapentin and 8.8% receiving placebo. The most common adverse events in the gabapentin group were drowsiness, fatigue, and dizziness. Interpretation Gabapentin demonstrated significant efficacy with an acceptable safety profile in treating cough in IPF. These findings support gabapentin as a potential treatment option for IPF-related cough. Clinical Trial Registration The study was registered with the Chinese Clinical Trial Registry (ChiCTR2100045202).
Background Mepolizumab and dupilumab are monoclonal antibodies targeting type 2 inflammation that are both approved as add-on maintenance treatment in patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype. Research Question What is the comparative efficacy of mepolizumab and dupilumab in reducing the risk of exacerbations and improving health-related quality of life in patients with COPD and an eosinophilic phenotype? Study Design and Methods This study used a robust matching-adjusted indirect comparison (MAIC) approach to compare pooled efficacy data from three Phase III, randomized, placebo-controlled COPD trials of mepolizumab (METREX [NCT02105948], METREO [NCT02105961], and MATINEE [NCT04133909]) with two trials of dupilumab (BOREAS [NCT03930732] and NOTUS [NCT04456673]). An indirect comparison was performed using MAIC, reweighting individual patient data from mepolizumab trials using propensity score-based methods to match the aggregate baseline characteristics of the dupilumab trial populations. To match the more restrictive eligibility criteria of the dupilumab trials, patients from the mepolizumab studies were included in this MAIC if they had blood eosinophil counts ≥300 cells/μL at screening, modified Medical Research Council scale grade ≥2, moderate-to-severe airflow limitation, and chronic bronchitis (CB) (defined by investigator assessment or St George’s Respiratory Questionnaire for COPD [SGRQ-C]). Outcomes included rate/risk of exacerbations and health-related quality of life (SGRQ-C). Results No statistically significant differences were observed in the reduction of the annualized rate of moderate/severe exacerbations (rate ratio [95% confidence interval]: 0.91 [0.60, 1.37] using investigator-assessed CB and 1.13 [0.80, 1.58] using SGRQ-C CB definition). No statistically significant differences were observed in SGRQ-C changes. Interpretation In this MAIC study, there were no statistically significant differences between mepolizumab and dupilumab in the magnitude of effect in reducing moderate/severe exacerbations and improving health-related quality-of-life outcomes.
BACKGROUND:Pulmonary function tests (PFTs) are essential for evaluating respiratory disease but are often accompanied by limited patient education. There is a lack of data describing how patients experience PFTs and what they need to feel prepared. Inadequate pretest counseling may contribute to anxiety, poor patient understanding, and resultant suboptimal test performance. RESEARCH QUESTION:What are patient experiences with PFTs, and how can these insights inform the content of a patient-centered educational pamphlet optimized for clinical use and ease of readability? STUDY DESIGN AND METHODS:A multiphase study was conducted at a large academic safety-net hospital. Initial pamphlet development drew on a targeted literature review, observation of PFTs, and firsthand PFT experience. Six patient focus groups, 1 clinician focus group, and 1 respiratory therapist interview were held. Transcripts underwent rapid content analysis to identify themes and refine the pamphlet iteratively. Readability of the final pamphlet was assessed with the Simple Measure of Gobbledygook (SMOG) and Flesch-Kincaid grade-level tools. RESULTS:Four major themes emerged: (1) emotional responses (anxiety, shame), (2) physical demands, (3) expectation-experience mismatches, and (4) clinician interactions. Patients reported inadequate pretest information about logistics and PFT maneuvers. They viewed the pamphlet favorably and suggested clearer wording, more visuals, and varied delivery formats, which informed revisions. The final pamphlet measured SMOG grade 6 and Flesch-Kincaid grade 7, aligning with American Medical Association recommendations. INTERPRETATION:These findings reveal a previously under-recognized problem: patients undergoing PFTs face substantial informational, emotional, and physical challenges that are rarely documented. A concise, user-centered pamphlet codeveloped with patient and clinician input may improve understanding and reduce anxiety. Future studies should evaluate the impact of such patient educational materials on PFT result quality and post-test patient outcomes.
BACKGROUND:Incidental emphysema on health-screening chest CT imaging is common, yet its prognostic significance in asymptomatic populations is characterized poorly. RESEARCH QUESTION:Is incidental emphysema on health screening chest CT imaging independently associated with all-cause mortality? STUDY DESIGN AND METHODS:This retrospective cohort comprised 41,291 adults undergoing chest CT imaging during routine health checkups in Korea (2002-2019). Emphysema was a binary variable from structured radiology reports, and the primary outcome was all-cause mortality via national death registry linkage. The primary analysis was a complete-case Cox model adjusted for age, sex, BMI, and smoking status; sensitivity analyses used multiple imputation, ever-smoking restriction, scanner-era adjustment, a time-varying exposure, and competing risks models. RESULTS:Emphysema was present in 3,774 participants (9.1%), rising from 2.6% in those who had never smoked to 14.6% in those who current smoked; over a median of 8.5 years, 284 deaths occurred. Emphysema was associated with all-cause mortality in the designated complete-case analysis (hazard ratio [HR], 1.54; 95% CI, 1.05-2.25), among those who had ever smoked after pack-years adjustment (HR, 1.63; 95% CI, 1.09-2.43), and when exposure was updated at repeat imaging (HR, 1.69; 95% CI, 1.18-2.41). Full-cohort pack-years imputation was not significant (HR, 1.36; 95% CI, 0.97-1.91), diluted by those who had never smoked, among whom no participant with emphysema died. An exploratory cancer signal (HR, 2.25) was concentrated in lung cancer (13 events). Adding emphysema to a smoking-inclusive model improved discrimination by ≤ 0.004. INTERPRETATION:Among those who had ever smoked, incidental emphysema on screening chest CT imaging was associated with mortality after adjustment for pack-years of smoking, although residual confounding because of smoking intensity cannot be excluded. After smoking history is known, the report adds almost nothing to discrimination and should not be used alone to stratify prognosis; we did not address whether it should prompt evaluation for undiagnosed COPD. In the full screening population, the association did not reach significance, but with 284 deaths, one-half the number needed for 80% power, that result is inconclusive, rather than negative.
BACKGROUND:Hyperglycemia is common in intensive care unit (ICU) patients and associated with increased mortality. Despite several randomized clinical trials within glucose management in critical illness, the effects of insulin treatment, and its timing, in patients with moderate hyperglycemia remain uncertain. RESEARCH QUESTION:In acutely admitted ICU patients with moderate hyperglycemia, does insulin treatment improve clinical outcomes and does timing of insulin initiation matter? STUDY DESIGN AND METHODS:We performed a multicenter target trial emulation using targeted minimum loss-based estimation. We included patients from four ICUs at Karolinska University Hospitals, Solna, Huddinge, from 2010 to 2021. We assessed the effect of early insulin treatment compared with delayed or no insulin treatment on 30-day all-cause mortality in acutely admitted adult ICU patients with moderate hyperglycemia (10 - 13.9 mmol/L). RESULTS:We included 5,755 patients with moderate hyperglycemia; 3,149 (54.7%) received early insulin therapy (intervention group) and 2,606 (45.3%) received delayed or no insulin therapy (control group). The adjusted 30-day mortality was 22.1% (95% CI 21.1 - 23.1) for patients receiving insulin within 6 hours and 24.4% (95% CI 23.5 - 25.4) for patients with later or no insulin treatment, corresponding to an absolute risk reduction of 2.3% (95% CI 1.1 - 3.6). Absolute risk was reduced by 7.7%-points (CI 95% 6.5 - 8.9) when insulin was initiated within 1 hour of the first episode of moderate hyperglycemia and by 6.6%-points (CI 95% 5.4 - 7.8) with initiation within 2 hours. This effect was modified in several subgroups. INTERPRETATIONS:In this target trial emulation, early insulin treatment of moderate hyperglycemia showed reduced mortality in acutely admitted adult ICU patients - particularly when insulin was initiated within 2 hours following hyperglycemia. These findings support further investigation in timing of insulin initiation.
BACKGROUND:Lung cancer screening offers an opportunity to enhance COPD detection among adults exposed to tobacco smoke; however, guidance on CT scan-based referral for spirometry is limited. RESEARCH QUESTION:Which low-dose CT scan emphysema threshold best identifies previously undiagnosed COPD in lung cancer screening patients, and does the addition of quantitative airway biomarkers enhance detection? STUDY DESIGN AND METHODS:In adults undergoing lung cancer screening, we performed spirometry to identify previously undiagnosed COPD, defined by airflow obstruction (FEV1/FVC < 0.70) in patients who currently smoke and patients who formerly smoked with ≥ 10 pack-years. We quantified emphysema extent, airway wall thickness (standardized square root wall area of airways with a theoretical internal perimeter of 10 mm), and airway branch count on low-dose CT scan using artificial intelligence-based software and combined these measures with clinical characteristics, mainly smoking history and dyspnea, to develop an ensemble tree-based machine-learning model (Extreme Gradient Boosting) for COPD detection. A sensitivity analysis using the lower limit of normal definition for FEV1/FVC was additionally performed. RESULTS:Among 5,014 screening patients with available spirometry, 1,115 had previously undiagnosed COPD, corresponding to a prevalence of 22.2%. In patients without known airway disease, emphysema alone at an optimized threshold of 5.1% showed moderate performance for COPD detection (area under the receiver operating characteristic curve [AUC], 0.69; 95% CI, 0.67-0.72; accuracy, 66%; positive predictive value [PPV], 44%), where 41% of patients exceeded this threshold and met criteria for confirmatory spirometry. An integrated model combining emphysema, standardized square root wall area of airways with a theoretical internal perimeter of 10 mm, airway branch count, and clinical characteristics significantly improved detection (AUC, 0.83; 95% CI, 0.80-0.86; accuracy, 78%; PPV, 59%) while reducing the proportion requiring confirmatory spirometry to 34%. In a sensitivity analysis using the lower limit of normal definition of COPD, the best-performing model achieved an AUC of 0.86 (95% CI, 0.83-0.89), accuracy of 84%, and PPV of 53%, while referring 22% for confirmatory spirometry. INTERPRETATION:Our results show that an integrated approach combining CT scan-derived airway biomarkers and clinical characteristics enables more efficient and targeted COPD detection within lung cancer screening programs. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT04913155; URL: www. CLINICALTRIALS:gov.
