The 100 most-cited articles in CHEST Journal, 2024

The American College of Chest Physicians (CHEST) Antithrombotic Therapy for Venous Thromboembolism Disease evidence-based guidelines are now updated in a more frequent, focused manner. Guidance statements from the most recent full guidelines and two subsequent updates have not been gathered into a single source. An international panel of experts with experience in prior antithrombotic therapy guideline development reviewed the 2012 CHEST antithrombotic therapy guidelines and its two subsequent updates. All guideline statements and their associated patient, intervention, comparator, and outcome questions were assembled. A modified Delphi process was used to select statements considered relevant to current clinical care. The panel further endorsed minor phrasing changes to match the standard language for guidance statements using the modified Grading of Recommendations, Assessment, Development, and Evaluations (ie, GRADE) format endorsed by the CHEST Guidelines Oversight Committee. The panel appended comments after statements deemed as relevant, including suggesting that statements be…

BACKGROUND: Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis. STUDY DESIGN AND METHODS: Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development, and Evaluation methodology. The guidelines were revised after public consultation. RESULTS: The panel made 14 recommendations on albumin use in adult…

BACKGROUND: Inhaled antibiotics are recommended conditionally by international bronchiectasis guidelines for the treatment of patients with bronchiectasis, but results of individual studies are inconsistent. A previous meta-analysis demonstrated promising results regarding the efficacy and safety of inhaled antibiotics in bronchiectasis. Subsequent publications have supplemented the existing body of evidence further in this area. RESEARCH QUESTION: To what extent do inhaled antibiotics demonstrate both efficacy and safety as a treatment option for adults with bronchiectasis? STUDY DESIGN AND METHODS: . Data were pooled through random-effects meta-analysis. RESULTS: was not changed with treatment. Evidence suggests little to no difference in adverse effects between groups (OR, 0.99; 95% CI, 0.75-1.30). Antibiotic-resistant organisms likely were increased by treatment. INTERPRETATION: In this systematic review and meta-analysis, inhaled antibiotics resulted in a slight reduction in exacerbations, a probable reduction in severe exacerbations, and a likely slight improvement in symptoms…

In this installment of the How I Do It series on severe asthma, we tackle the clinical conundrum of choosing the right biologic for the right patient with severe asthma. With six biologics now approved for use in this area comprising four different targeting strategies (anti-Ig E: omalizumab; anti-IL-5 and anti-IL-5-receptor: mepolizumab, reslizumab, and benralizumab; anti-IL-4-receptor: dupilumab; anti-thymic stromal lymphopoietin: tezepelumab), this question is increasingly complex. Recognizing that no head-to-head trial has compared biologics, we based our review on the expected effects of inhibiting different aspects of type 2 airway inflammation, supported whenever possible by clinical trial and real-world data. We use four variations of a case of severe uncontrolled asthma to develop concepts and considerations introduced in the previous installment ("Workup of Severe Asthma") and discuss pregnancy-related, biomarker-related, comorbidity-related, and corticosteroid dependency-related considerations when choosing a biologic. The related questions of deciding when, why, and how…

BACKGROUND: Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated. RESEARCH QUESTION: Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease? STUDY DESIGN AND METHODS: In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality. RESULTS: Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients…

Artificial intelligence (AI) is increasingly being used in health care. Without an ethically supportable, standard approach to knowing when patients should be informed about AI, hospital systems and clinicians run the risk of fostering mistrust among their patients and the public. Therefore, hospital leaders need guidance on when to tell patients about the use of AI in their care. In this article, we provide such guidance. To determine which AI technologies fall into each of the identified categories (no notification or no informed consent [IC], notification only, and formal IC), we propose that AI use-cases should be evaluated using the following criteria: (1) AI model autonomy, (2) departure from standards of practice, (3) whether the AI model is patient facing, (4) clinical risk introduced by the model, and (5) administrative burdens. We take each of these in turn, using a case example of AI in health care to illustrate our proposed framework. As AI becomes more commonplace in health care, our proposal may serve as a starting point for creating consensus on standards for…

BACKGROUND: Pulmonary hypertension (PH) is a heterogeneous disease with a poor prognosis. Accurate risk stratification is essential for guiding treatment decisions in pulmonary arterial hypertension (PAH). Although various risk models have been developed for PAH, their comparative prognostic potential requires further exploration. Additionally, the applicability of risk scores in PH groups beyond group 1 remains to be investigated. RESEARCH QUESTION: Are risk scores originally developed for PAH predictive in PH groups 1 through 4? STUDY DESIGN AND METHODS: We conducted a comprehensive analysis of outcomes among patients with incident PH enrolled in the multicenter worldwide Pulmonary Vascular Research Institute GoDeep meta-registry. Analyses were performed across PH groups 1 through 4 and further subgroups to evaluate the predictive value of PAH risk scores, including the Registry to Evaluate Early and Long-Term PAH Disease Mangement (REVEAL) Lite 2, REVEAL 2.0, European Society of Cardiology/European Respiratory Society 2022, Comparative, Prospective Registry of Newly Initiated…

BACKGROUND: Blood products frequently are administered to critically ill patients. Considering recent trials and practice variability, a comprehensive review of current evidence was deemed essential to offer pertinent guidance to critical care practitioners. This American College of Chest Physicians (CHEST) guidelines panel examined the literature on RBC transfusions among critically ill patients overall and specific subgroups, including patients with gastrointestinal bleeding, acute coronary syndrome (ACS), cardiac surgery, isolated troponin elevation, and septic shock, to provide evidence-based recommendations. STUDY DESIGN AND METHODS: A panel of experts developed six Population, Intervention, Comparator, and Outcome questions addressing RBC transfusions in critically ill patients and performed a comprehensive evidence review. The panel applied the Grading of Recommendations, Assessment, Development, and Evaluations approach to assess the certainty of evidence and to formulate and grade recommendations. A modified Delphi technique was used to reach consensus on the…

TOPIC IMPORTANCE: Stroke is the second-leading cause of death worldwide. OSA is an independent risk factor for stroke and is associated with multiple vascular risk factors. Poststroke OSA is prevalent and closely linked with various stroke subtypes, including cardioembolic stroke and cerebral small vessel disease. Observational studies have shown that untreated poststroke OSA is associated with an increased risk of recurrent stroke, mortality, poorer functional recovery, and longer hospitalizations. REVIEW FINDINGS: Poststroke OSA tends to be underdiagnosed and undertreated, possibly because patients with stroke and OSA present atypically compared with the general population with OSA. Objective testing, such as the use of ambulatory sleep testing or in-laboratory polysomnography, is recommended for diagnosing OSA. The gold standard for treating OSA is CPAP therapy. Randomized controlled trials have shown that treatment of poststroke OSA using CPAP improves nonvascular outcomes such as cognition and neurologic recovery. However, findings from randomized controlled trials that have…

BACKGROUND: Antibiotics with extended anaerobic coverage are used commonly to treat aspiration pneumonia, which is not recommended by current guidelines. RESEARCH QUESTION: In patients admitted to hospital for community-acquired aspiration pneumonia, does a difference exist between antibiotic therapy with limited anaerobic coverage (LAC) vs antibiotic therapy with extended anaerobic coverage (EAC) in terms of in-hospital mortality and risk of Clostridioides difficile colitis? STUDY DESIGN AND METHODS: We conducted a multicenter retrospective cohort study across 18 hospitals in Ontario, Canada, from January 1, 2015, to January 1, 2022. Patients were included if the physician diagnosed aspiration pneumonia and prescribed guideline-concordant first-line community-acquired pneumonia parenteral antibiotic therapy to the patient within 48 h of admission. Patients then were categorized into the LAC group if they received ceftriaxone, cefotaxime, or levofloxacin. Patients were categorized into the EAC group if they received amoxicillin-clavulanate, moxifloxacin, or any of ceftriaxone,…

BACKGROUND: Positive end-expiratory pressure (PEEP) can potentially modulate inspiratory effort (ΔPes), which is the major determinant of self-inflicted lung injury. RESEARCH QUESTION: Does high PEEP reduce ΔPes in patients with moderate-to-severe ARDS on assisted ventilation? STUDY DESIGN AND METHODS: O + synchronous (pressure support ventilation [PSV]) or asynchronous (pressure-controlled intermittent mandatory ventilation [PC-IMV]) inspiratory assistance. ΔPes and respiratory system, lung, and chest wall mechanics were assessed with esophageal manometry and occlusions. PEEP-induced alveolar recruitment and overinflation, lung dynamic strain, and tidal volume distribution were assessed with electrical impedance tomography. RESULTS: O; P = .24; pressure-controlled intermittent mandatory ventilation: median, 20; IQR, 18-23 vs median, 19; IQR, 17-25; P = .67, respectively). Similarly, respiratory system and transpulmonary driving pressures, tidal volume, lung/chest wall mechanics, and pendelluft extent were not different between study phases. High PEEP resulted in lower or higher…

BACKGROUND: Breathlessness shares aging mechanisms with frailty and sarcopenia. RESEARCH QUESTION: Are frailty and sarcopenia associated with breathlessness itself? STUDY DESIGN AND METHODS: We analyzed data from a population-based, prospective cohort study of 780 community-dwelling older adults. Breathlessness was defined using the modified Medical Research Council dyspnea scale (≥ 2 points) and the COPD Assessment Test (≥ 10 points). Frailty was defined by frailty index (FI); frailty phenotype; and fatigue, resistance, ambulation, illness, and weight loss (FRAIL) questionnaire results. Sarcopenia was defined by the Asian Working Group for Sarcopenia in 2019. Sarcopenia phenotype score quantified the number of criteria met. The associations of frailty and sarcopenia with breathlessness were evaluated by logistic regression analyses. Adjusted ORs (aORs) were calculated, accounting for age, sex, chronic airway disease, smoking status, BMI, lung functions, socioeconomic status (living alone, income, education), comorbid conditions (hypertension, diabetes, malignancy, myocardial…

BACKGROUND: For decades, the incidence and clinical characteristics of Pneumocystis jirovecii colonization in patients with severe pneumonia was unclear. RESEARCH QUESTION: What are the clinical features and outcomes associated with P jirovecii colonization in individuals diagnosed with severe pneumonia? STUDY DESIGN AND METHODS: In this multicenter, retrospective, matched study, patients with severe pneumonia who underwent bronchoalveolar lavage clinical metagenomics from 2019 to 2023 in the ICUs of 17 medical centers were enrolled. Patients were diagnosed based on clinical metagenomics, pulmonary CT scans, and clinical presentations. Clinical data were collected retrospectively, and according to propensity score matching and Cox multivariate regression analysis, the prognosis of patients with P jirovecii colonization was compared with that of patients who were P jirovecii-negative. RESULTS: A total of 40% of P jirovecii-positive patients are considered to have P jirovecii colonization. The P jirovecii colonization group had a higher proportion of patients with immunosuppression…

TOPIC IMPORTANCE: COPD is a complex, heterogeneous lung disease characterized by persistent airflow limitation secondary to airways and parenchymal abnormalities, and respiratory symptoms, including dyspnea, fatigue, chronic cough, and sputum production. Cigarette smoke exposure is a major contributor to COPD; however, inhalation of toxic particles and other environmental and host factors can contribute to its genesis. Over time, the clinical course is frequently punctuated by exacerbations that further accelerate lung function decline and increase exacerbation risk. Despite current optimal therapy, many patients remain symptomatic, have exacerbations, and have increased morbidity, mortality, and health care costs. This review focuses on current knowledge of COPD pathophysiology, the role of inflammatory mechanisms, and the potential use of biologics to modulate these mechanisms. REVIEW FINDINGS: The inflammatory response in COPD includes both type 1 and type 2 immune cells. Type 2 inflammation is suggested by eosinophilia in a significant proportion of patients with COPD. Studies…

TOPIC IMPORTANCE: Interstitial lung diseases (ILDs) represent a broad group of heterogeneous parenchymal lung diseases. Some ILDs progress, causing architectural distortion and pulmonary fibrosis, and thus are called fibrotic ILDs. Recent studies have shown a beneficial effect of antifibrotic therapy in fibrotic ILDs other than idiopathic pulmonary fibrosis (IPF) that manifest progressive pulmonary fibrosis (PPF). However, it remains challenging to predict which patients with fibrotic ILDs will demonstrate PPF. Precision medicine approaches could identify patients at risk for progression and guide treatment in patients with IPF or PPF. REVIEW FINDINGS: Multiple biomarkers able to highlight disease susceptibility risk, to provide an accurate diagnosis, and to prognosticate or assess treatment response have been identified. Advances in precision medicine led to the identification of endotypes that could discriminate patients with different fibrotic ILDs or patients with different disease courses. Importantly, recent studies have shown that particular compounds were efficacious only in…

BACKGROUND: The epidemiology of nontuberculous mycobacteria (NTM) infections is not well described. In this study, we sought to determine the incidence and prevalence of NTM infections and focus on social risk factors. In addition, we describe people with pulmonary and extrapulmonary NTM. RESEARCH QUESTION: What are the incidence and prevalence of NTM in Denmark, and what are the characteristics of the affected patients? STUDY DESIGN AND METHODS: This is a nationwide retrospective register-based cohort study in Denmark. Adult patients in the Danish national registers who received a diagnosis of NTM disease from 2000 to 2017 were classified as having either pulmonary or extrapulmonary NTM disease. RESULTS: We identified 1,146 adults with an NTM diagnosis. Of these, 661 patients had pulmonary NTM, of whom 50.4% were male, whereas 485 had extrapulmonary NTM, of whom 59.6% were male. The median age (interquartile range) was 66 (18) years and 57 (32) years, respectively. The yearly incidence rate per 100,000 increased between 2000 and 2017 for both pulmonary NTM (0.4 to 1.3) and…

Background Asthma remission is a potential treatment goal. Research question Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared to placebo? Study Design and Methods This secondary analysis used data from the AMAZES clinical trial – a double-blind placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids (OCS) during the previous six months evaluated at 12 months and Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (post-bronchodilator FEV1≥80% or post-bronchodilator FEV1≤5% decline from baseline) and complete remission (sputum eosinophils<3% plus the above criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified. Results 335 participants (41.5% male; median…

BACKGROUND: Preserved ratio impaired spirometry (PRISm) and restrictive spirometric pattern (RSP) are often considered interchangeable in identifying restrictive impairment in spirometry. RESEARCH QUESTION: Do PRISm and RSP have different individual associations with risk factors, morbidity, and mortality? STUDY DESIGN AND METHODS: /FVC ≥ LLN and FVC < LLN. We compared the associations of PRISm and RSP to airflow obstruction and normal spirometry, both as mutually (PRISm alone, RSP alone) and nonmutually exclusive (PRISm, RSP) categories, adjusting for age, BMI, smoking, and education. We also conducted sensitivity analyses using Global Initiative for Chronic Obstructive Lung Disease criteria to define spirometric abnormalities. RESULTS: The prevalence of the mutually exclusive spirometric patterns was as follows: normal 82.4%, obstruction 11.0%, PRISm alone 1.4%, RSP alone 1.7%, and PRISm + RSP 3.5%. PRISm alone patients frequently had obesity (11.2%) and had active or previous tobacco use, commonly reporting cough, phlegm, wheeze, asthma, and bronchitis. RSP alone patients had…

TOPIC IMPORTANCE: Acute pulmonary embolism (PE) is a common disease encountered by pulmonologists, cardiologists, and critical care physicians throughout the world. For patients with high-risk acute PE (defined by systemic hypotension) and intermediate high-risk acute PE (defined by the absence of systemic hypotension, but the presence of numerous other concerning clinical and imaging features), intensive care often is necessary. Initial management strategies should focus on optimization of right ventricle (RV) function while decisions about advanced interventions are being considered. REVIEW FINDINGS: We reviewed the existing literature of various vasoactive agents, IV fluids and diuretics, and pulmonary vasodilators in both animal models and human trials of acute PE. We also reviewed the potential complications of endotracheal intubation and positive pressure ventilation in acute PE. Finally, we reviewed the data of venoarterial extracorporeal membrane oxygenation use in acute PE. The above interventions are discussed in the context of the underlying pathophysiologic features of…

BACKGROUND: Acute exacerbations (AEs) of COPD are increasingly recognized as episodes of heightened risk of cardiovascular events. It is not known whether exacerbation history is differentially associated with future myocardial infarction (MI) or pulmonary embolism (PE). RESEARCH QUESTION: Is the number and severity of AEs of COPD associated with increased risk of MI or PE in a real-life cohort of patients with COPD? STUDY DESIGN AND METHODS: We identified a cohort of 66,422 patients (≥ 30 years of age) with a primary diagnosis of COPD in the Swedish National Airway Register from January 2014 to June 2022, with complete data on lung function. Patients were classified by moderate (prescription of oral corticosteroids) and severe (hospitalization) exacerbations the year before index date and were followed until December 2022 for hospitalization or death from MI or PE, corresponding to > 265,000 patient-years, with a maximum follow-up time of 9 years. Competing risk regression, according to the Fine-Gray model, was used to calculate subdistribution hazard ratios with 95% CIs. RESULTS:…

BACKGROUND: Exacerbations in COPD can be life-threatening and can lead to irreversible declines in lung function and quality of life. Medications that reduce exacerbation burden are an unmet need, because exacerbations put patients at risk of more exacerbations and decrease quality of life. Ensifentrine is a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 with demonstrated nonsteroidal antiinflammatory activity and bronchodilatory effects. RESEARCH QUESTION: Does ensifentrine reduce the rate or risk of COPD exacerbations? STUDY DESIGN AND METHODS: A prespecified, pooled analysis of the phase 3 clinical trials Ensifentrine as a Novel Inhaled Nebulized COPD Therapy (ENHANCE)-1 (ClinicalTrials.gov Identifier: NCT04535986) and ENHANCE-2 (ClinicalTrials.gov Identifier: NCT04542057) was conducted to assess the effect of ensifentrine on exacerbation rate and risk (time to first exacerbation). The trials included symptomatic patients aged 40 to 80 years with moderate to severe COPD who received 3 mg twice-daily ensifentrine over 24 weeks or placebo. Subgroup analyses…

BACKGROUND: Previous studies have shown the importance of frailty in patients with fibrotic interstitial lung disease (ILD). RESEARCH QUESTION: Is the Clinical Frailty Scale (CFS) a valid tool to improve risk stratification in patients with fibrotic ILD? STUDY DESIGN AND METHODS: Patients with fibrotic ILD were included from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. The CFS was assessed using available information from initial ILD clinic visits. Patients were stratified into fit (CFS score 1-3), vulnerable (CFS score 4), and frail (CFS score 5-9) subgroups. Cox proportional hazards and logistic regression models with mixed effects were used to estimate time to death or lung transplantation. A derivation and validation cohort was used to establish prognostic performance. Trajectories of functional tests were compared using joint models. RESULTS: Of the 1,587 patients with fibrotic ILD, 858 (54%) were fit, 400 (25%) were vulnerable, and 329 (21%) were frail. Frailty was a risk factor for early mortality (hazard ratio, 5.58; 95% CI, 3.64-5.76, P < .001) in…

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by the malfunction of motile cilia and a specific etiology of adult bronchiectasis of unknown prevalence. A better understanding of the clinical phenotype of adults with PCD is needed to identify individuals for referral to diagnostic testing. RESEARCH QUESTION: What is the frequency of PCD among adults with bronchiectasis; how do people with PCD differ from those with other etiologies; and which clinical characteristics are independently associated with PCD? STUDY DESIGN AND METHODS: ), 58 (breathlessness), 26 (pulmonary exacerbations), and two patients (BMI), respectively; and identified predictive variables from baseline data using multivariate logistic regression analysis. RESULTS: We consecutively recruited 1,000 patients from 38 centers across all levels of the German health care system. Overall, PCD was the fifth most common etiology of bronchiectasis in 87 patients (9%) after idiopathic, postinfective, COPD, and asthma. People with PCD showed a distinct clinical phenotype. In multivariate…

BACKGROUND: The clinical phenotype of patients with idiopathic pulmonary arterial hypertension (IPAH) has changed. Whether subgroups of patients with IPAH have different vascular phenotypes is a subject of debate. RESEARCH QUESTION: What are the histologic patterns and their clinical correlates in patients with a diagnosis of IPAH or hereditary pulmonary arterial hypertension? STUDY DESIGN AND METHODS: In this this cross-sectional registry study, lung histology of 50 patients with IPAH was assessed qualitatively by two experienced pathologists. In addition, quantitative analysis by means of histopathologic morphometry using immunohistochemistry was performed. Histopathologic characteristics were correlated with clinical and hemodynamic parameters. RESULTS: In this cohort of 50 patients with IPAH, a plexiform vasculopathy was observed in 26 of 50 patients (52%), whereas 24 of 50 patients (48%) showed a nonplexiform vasculopathy. The nonplexiform vasculopathy was characterized by prominent pulmonary microvascular (arterioles and venules) remodeling and vascular rarefaction. Although…

The small airways comprise generations 8 to 23 of the bronchial tree, consist of airways with an internal diameter < 2 mm, and are classically difficult to assess and treat in persistent asthma. Small airways dysfunction (SAD) is integral to the asthma management paradigm because it is associated with poorer symptom control and greater levels of type 2 inflammation, and it has been proposed as a potentially treatable asthma trait. Although identification of SAD based on oscillometry has been found to be clinically useful in managing asthma, very few physicians, including specialists, use this technique as part of standard or adjunct evaluation of lung function to diagnose asthma, grade severity of airway obstruction, ascertain disease control or the risk for future exacerbations, or to make management decisions. To rectify the unrecognized value of oscillometry in the asthma community, a consortium of authors who are investigators with knowledge and experience of oscillometry wished to address the most important clinical questions raised by our colleagues who are considering using…

TOPIC IMPORTANCE: Diffuse cystic lung diseases (DCLDs) represent a group of pathophysiologically heterogeneous entities that share a common radiologic phenotype of multiple thin-walled pulmonary cysts. DCLDs differ from the typical fibroinflammatory interstitial lung diseases in their epidemiology, clinical presentation, molecular pathogenesis, and therapeutic approaches, making them worthy of a distinct classification. The importance of timely and accurate identification of DCLDs is heightened by the impact on patient management including recent discoveries of targeted therapeutic approaches for some disorders. REVIEW FINDINGS: This article offers a practical framework for evaluating patients with DCLD, indicating the most appropriate and current diagnostic and management approaches. We focus on the DCLDs that are most likely to be encountered by practicing pulmonologists: lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, Birt-Hogg-Dubé syndrome, and lymphoid interstitial pneumonia. Chest CT scan is the most informative noninvasive diagnostic modality to identify…

Abstract Background The varied treatment response to inhaled corticosteroids (ICS) in COPD, and the increased risk of pneumonia necessitate a personalised ICS approach. This is informed by blood eosinophil count (BEC), which predicts ICS treatment response. This post-hoc analysis evaluates the ability of different BEC measurements to predict ICS treatment response. BEC measured either on or off ICS treatment, and BEC change during ICS treatment were investigated. Methods FLAME, a 52-week, double-blind RCT compared LABA/LAMA versus LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing pre and post run-in period BEC to represent BEC on and off ICS, respectively. In this post-hoc analysis, we revisited outcome data, exploring how the three BEC biomarkers interacted with treatment response to the ICS containing regimen. Results Our study confirms that LABA/LAMA combination is superior, or at least non-inferior, to LABA/ICS in curbing exacerbations for most FLAME participants. Lower BEC off and BEC on ICS and lack…

BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbation rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939…

Background ARDS is a heterogeneous condition with two subphenotypes identified by different methodologies. Our group similarly identified two ARDS subphenotypes using nine routinely available clinical variables. However, whether these are associated with differential response to treatment has yet to be explored. Research Question Are there differential responses to positive end-expiratory pressure (PEEP) strategies on 28-day mortality according to subphenotypes in adult patients with ARDS? Study Design and Methods We evaluated data from two prior ARDS trials (Higher vs Lower Positive End-Expiratory Pressures in Patients With the ARDS [ALVEOLI] and the Alveolar Recruitment in ARDS Trial [ART]) that compared different PEEP strategies. We classified patients into one of two subphenotypes as described previously. We assessed the differential effect of PEEP with a Bayesian hierarchical logistic model for the primary outcome of 28-day mortality. Results We analyzed data from 1,559 patients with ARDS. Compared with lower PEEP, a higher PEEP strategy resulted in higher 28-day mortality in…

A diagnosis of interstitial lung diseases (ILD) can be challenging, and the identification of an associated connective tissue disease (CTD) is crucial to estimate prognosis and to establish the optimal treatment approach. Diagnostic delay, limited expertise, and fragmented care are barriers that impede the delivery of comprehensive health care for patients with rare, complex, and multiorgan diseases such as CTD and ILD. In this article, we present our perspective on the interdisciplinary diagnosis and interprofessional treatment of patients with ILD and suspected CTD or CTD at risk of ILD. We outline the structure of our service, delineating the roles and responsibilities of the team members. Additionally, we provide an overview of our patient population, including diagnostic approaches and specific treatments, and illustrate a patient case. Furthermore, we focus on specific benefits and challenges of joint interdisciplinary and interprofessional patient consultations. The importance of rheumatology and pulmonology assessments in specific patient populations is emphasized. Finally,…

Sepsis causes more than a quarter million deaths among hospitalized adults in the United States each year. Although most cases of sepsis are present on admission, up to one-quarter of patients with sepsis develop this highly morbid and mortal condition while hospitalized. Compared with patients with community-onset sepsis (COS), patients with hospital-onset sepsis (HOS) are twice as likely to require mechanical ventilation and ICU admission, have more than two times longer ICU and hospital length of stay, accrue five times higher hospital costs, and are twice as likely to die. Patients with HOS differ from those with COS with respect to underlying comorbidities, admitting diagnosis, clinical manifestations of infection, and severity of illness. Despite the differences between these patient populations, patients with HOS sepsis are understudied and warrant expanded investigation. Here, we outline important knowledge gaps in the recognition and management of HOS in adults and propose associated research priorities for investigators. Of particular importance are questions regarding…

TOPIC IMPORTANCE: Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder most commonly due to a single G to A point mutation (E342K), leading to debilitating lung and/or liver disorders and is associated with increased mortality. The E342K point mutation causes a conformational change of the AAT protein resulting in its retention in liver hepatocytes. This reduces AAT secretion into the serum resulting in higher protease activities due to the lack of inhibition from AAT, causing damage to healthy lung tissue. The current standard of care for lung manifestations involves weekly IV augmentation therapy and is considered suboptimal for these patients. Furthermore, there is currently no approved treatment for liver manifestations. The unmet medical need for patients with AAT deficiency remains high, and new treatment options are needed to treat the underlying disease etiology. REVIEW FINDINGS: Advances in genomic medicines may enable treatment by editing the DNA or RNA sequence to produce wild-type AAT instead of the mutated AAT caused by the E342K mutation. One approach can be…

BACKGROUND: Chest radiographs (CXRs) are still of crucial importance in primary diagnostics, but their interpretation poses difficulties at times. RESEARCH QUESTION: Can a convolutional neural network-based artificial intelligence (AI) system that interprets CXRs add value in an emergency unit setting? STUDY DESIGN AND METHODS: A total of 563 CXRs acquired in the emergency unit of a major university hospital were retrospectively assessed twice by three board-certified radiologists, three radiology residents, and three emergency unit-experienced nonradiology residents (NRRs). They used a two-step reading process: (1) without AI support; and (2) with AI support providing additional images with AI overlays. Suspicion of four suspected pathologies (pleural effusion, pneumothorax, consolidations suspicious for pneumonia, and nodules) was reported on a five-point confidence scale. Confidence scores of the board-certified radiologists were converted into four binary reference standards of different sensitivities. Performance by radiology residents and NRRs without AI support/with AI…

Asthma is a common, multifaceted respiratory disease with a major impact on quality of life. Despite increased insights into mechanisms underlying various asthma phenotypes and endotypes and the availability of targeted biologic treatment options, the disease remains uncontrolled in a substantial proportion of patients with risk of exacerbations, requiring systemic corticosteroids, and with progressive disease. Current international guidelines advocate for a personalized management approach to patients with uncontrolled severe asthma. The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) asthma expert panel was convened to discuss strategies to optimize asthma care and to prevent systemic corticosteroid overuse and disease progression. In this meeting report, we summarize current concepts and recommendations and provide a rationale to implement personalized asthma management at earlier stages of the disease. The ultimate goal is to move away from the current one-size-fits-most concept, which focuses on a symptom-driven treatment strategy, and shift…

Background Small airways obstruction (SAO) is common in general populations. It has been associated with respiratory symptoms, cardiometabolic diseases, and progression to COPD over time. Whether SAO predicts mortality is largely unknown. Research Question Is spirometry-defined SAO associated with increased mortality? Methods Data were analyzed from 252,877 adult participants, aged 40 to 69 years at baseline, in the UK Biobank who had provided good-quality spirometry measurements. SAO was defined as the ratio of the forced expiratory volume in 3 s to the forced expiratory volume in 6 s less than the lower limit of normal. SAO was considered to be isolated if present when the FEV 1 /forced expiratory volume in 6 s ratio was normal (ie, greater than the lower limit of normal). A multivariable Cox regression model was used to assess the association of SAO, and isolated SAO, with all-cause and disease-specific mortality. Sex differences were investigated in these associations, and the primary analysis was repeated, excluding those who ever smoked. All models were adjusted for potential…

BACKGROUND: Sepsis is the most common cause of acute kidney injury (AKI) in critically ill patients. Four phenotypes (α, β, γ, δ) for sepsis, which have different outcomes and responses to treatment, were described using routine clinical data in the electronic health record. RESEARCH QUESTION: Do the frequencies of AKI, acute kidney disease (AKD), chronic kidney disease (CKD), and AKI on CKD differ by sepsis phenotype? STUDY DESIGN AND METHODS: This was a secondary analysis of a randomized clinical trial of early resuscitation, including patients with septic shock at 31 sites. After excluding patients with end-stage kidney disease and missing data, we determined frequencies of the following clinical outcomes: AKI (defined within 24 h as Kidney Disease: Improving Global Outcomes stages 2 or 3 or stage 1 with tissue inhibitor of metalloproteinases-2 × insulin-like growth factor binding protein 7 value of > 2.0), CKD, and AKD (persistence of AKI at any stage on day 7 after enrollment) across four phenotypes. We performed multivariable logistic regression to assess the risk-adjusted…

Background Positional OSA (POSA) is a recognized subtype of OSA that exhibits distinct endotypic characteristics when compared with nonpositional OSA (NPOSA). The basis for the disparity in endotypes between these subtypes remains poorly understood. Research Question (1) Do individuals with NPOSA and POSA have different underlying OSA endotypes? (2) Which endotypic characteristics are critical in determining NPOSA and POSA severity? Study Design and Methods Within the Shanghai Sleep Health Study cohort, individuals with OSA were recruited and classified as having POSA or NPOSA. Endotypes were calculated using polysomnography. Results Endotype analysis was conducted in 1,036 individuals with OSA. Compared with individuals with NPOSA, those with POSA had lower loop gain calculated during all sleep stages and all sleep positions (0.55; interquartile range [IQR], 0.46-0.66 vs 0.68, IQR, 0.52-0.90; P < .001), lower arousal threshold calculated during all sleep stages and all sleep positions (ArTH All ) (138.67; IQR, 118.94-180.87 percentage of the eupneic ventilation [%Veupnea] vs…

BACKGROUND: It remains uncertain for how long pure ground-glass nodules (pGGNs) detected on low-dose CT (LDCT) imaging should be followed up. Further studies with longer follow-up periods are needed to determine the optimal follow-up duration for pGGNs. RESEARCH QUESTION: What is the percentage of enlarging nodules among pGGNs that have remained stable for 10 years? STUDY DESIGN AND METHODS: This was a retrospective cohort study originating from participants with pGGNs detected on LDCT scans between 1997 and 2006 whose natural courses were reported in 2013. We re-analyzed all the follow-up data until July 2022. The study participants were followed up per our institutional guidelines until they were no longer a candidate for definitive treatment. The growth of the pGGNs was defined as an increase in the diameter of the entire nodule by ≥ 2 mm or the appearance of new solid portions within the nodules. RESULTS: A total of 89 patients with 135 pGGNs were followed up for a median of 193 months. Of 135 pGGNs, 23 (17.0%) increased in size, and the median time to the first detection of a…

BACKGROUND: Microscopy is currently the gold standard to differentiate BAL fluid (BALF) leukocytes. However, local expertise for microscopic BALF leukocyte differentiation is often unavailable in clinical practice. RESEARCH QUESTION: Can automated flow cytometry be used instead of microscopy to differentiate BALF leukocytes? STUDY DESIGN AND METHODS: A new automated flow cytometric method for BALF leukocyte differentiation, using four antibodies (anti-CD45, anti-CD66b, anti-HLA-DR, anti-CD52) given to human BALF in one tube, was developed and prospectively validated in 745 unselected subsequent BALF samples from patients with interstitial lung diseases (455 patients), infectious diseases (196 patients), and other diseases (94 patients). Flow cytometry and traditional microscopy were performed by separate investigators in a double-anonymized fashion. Results were compared using Spearman correlation, Deming regression, and Bland-Altman analysis. RESULTS: There was a strong correlation between flow cytometric and microscopic results regarding macrophage/monocyte, lymphocyte,…

BACKGROUND: This scoping review was conducted to provide an overview of the evidence of point-of-care lung ultrasound (LUS) in emergency medicine. By emphasizing clinical topics, time trends, study designs, and the scope of the primary outcomes, a map is provided for physicians and researchers to guide their future initiatives. RESEARCH QUESTION: Which study designs and primary outcomes are reported in published studies of LUS in emergency medicine? STUDY DESIGN AND METHODS: We performed a systematic search in the PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library databases for LUS studies published prior to May 13, 2023. Study characteristics were synthesized quantitatively. The primary outcomes in all papers were categorized into the hierarchical Fryback and Thornbury levels. RESULTS: A total of 4,076 papers were screened and, following selection and handsearching, 406 papers were included. The number of publications doubled from January 2020 to May 2023 (204 to 406 papers). The study designs were primarily observational (n = 375 [92%]), followed by randomized (n…

BACKGROUND: Electromagnetic stimulation of the phrenic nerve induces diaphragm contractions, but no coils for clinical use have been available. We recently demonstrated the feasibility of ventilation using bilateral transcutaneous noninvasive electromagnetic phrenic nerve stimulation (NEPNS) before surgery in lung-healthy patients with healthy weight in a dose-dependent manner. RESEARCH QUESTION: Is NEPNS feasible in critically ill patients in an ICU setting? STUDY DESIGN AND METHODS: This feasibility nonrandomized controlled study aimed to enroll patients within 36 h of intubation who were expected to remain ventilated for ≥ 72 h. The intervention group received 15-min bilateral transcutaneous NEPNS bid, whereas the control group received standard care. If sufficient, NEPNS was used without pressure support to ventilate the patient; pressure support was added if necessary to ventilate the patient adequately. The primary outcome was feasibility, measured as time to find the optimal stimulation position. Further end points were sessions performed according to the protocol or allowing…

Background COPD inhaler regimens should be appropriate for the patient's peak inspiratory flow (PIF) and should ideally consist of single or similar device(s). Research Questions In a subspecialized COPD clinic: (1) What is the prevalence of patients with suboptimal PIF and with inappropriate device(s) for measured PIF? (2) Are there patient-related risk factors associated with suboptimal PIF? (3) What is the prevalence of patients with non-single inhaler therapy (SIT)/nonsimilar devices? (4) Does point-of-care PIF affect clinical decision-making? Study Design and Methods In this single-center real-world observational study, PIF was measured systematically at every outpatient visit in a subspecialized COPD clinic, and point-of-care results were provided to the clinician. Coprimary outcomes were the prevalence of outpatients with suboptimal PIF and with inappropriate devices for measured PIF. Secondary outcomes were patient-related risk factors associated with suboptimal PIF, the prevalence of non-SIT/nonsimilar devices, the prevalence of regimens consisting of either inappropriate…

Background Although it is generally accepted that aerobic exercise training does not change lung structure or function, some work suggests that greater pulmonary vascular structure and function are associated with higher exercise capacity (peak rate of oxygen consumption [ V ˙ o 2 peak]). Research Question Is there a cross-sectional association between the pulmonary vasculature and V ˙ o 2 peak? We hypothesized that those with higher CT blood vessel volumes and pulmonary diffusing capacity for carbon monoxide (Dlco) would have higher V ˙ o 2 peak, independent of airflow limitation. Study Design and Methods Participants from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study were categorized as follows: participants with normal spirometry who had never smoked (n = 263), participants with normal spirometry who had ever smoked (n = 407), and COPD: individuals with spirometric airflow obstruction (n = 334). Total vessel volume (TVV), volume for vessels < 5 mm 2 in cross-sectional area (BV5), and volume for vessels between 5 and 10 mm 2 in cross-sectional area (BV5-10) were…

Significant discussion in the medical literature of the environmental impact of respiratory inhaler propellants1-3 has led some health care systems to incentivize switching patients to lower global warming potential inhalers to target reductions in greenhouse gas emissions.4 However, unsupervised inhaler switching has adverse patient consequences,5,6 especially because respiratory health care professionals (HCPs) lack knowledge in inhaler use.7 This research aimed to gather HCP and asthma/COPD patient priorities when prescribing or choosing an inhaler device for medical, nonmedical, and environmental reasons.

BACKGROUND: The healthy adherer effect has gained increasing attention as a potential source of bias in observational studies examining the association of positive airway pressure (PAP) adherence with health outcomes in OSA. RESEARCH QUESTION: Is adherence to PAP associated with healthy behaviors and health care resource use prior to device prescription? STUDY DESIGN AND METHODS: Data from the Institut de Recherche en Santé Respiratoire (IRSR) des Pays de la Loire Sleep Cohort were linked to health administrative data to identify proxies of heathy behaviors, including adherence to cardiovascular (CV) drugs (medical possession ratio), cancer screening tests, influenza vaccination, alcohol and smoking consumption, and drowsiness-related road accidents during the 2 years preceding PAP onset in patients with OSA. Multivariable regression analyses were conducted to evaluate the association of heathy behaviors with subsequent PAP adherence. Health care resource use was evaluated according to subsequent PAP adherence. RESULTS: We included 2,836 patients who had started PAP therapy between…

BACKGROUND: COPD management is guided by the respiratory symptom burden, assessed using the modified Medical Research Council (mMRC) scale, the COPD Assessment Test (CAT), or both. RESEARCH QUESTION: What are the abilities of mMRC and CAT to detect abnormally high exertional breathlessness on incremental cardiopulmonary cycle exercise testing (CPET) in people with COPD? STUDY DESIGN AND METHODS: to FVC ratio of < 0.70 after bronchodilator administration and ≥ 10 pack-years of smoking from the Canadian Cohort Obstructive Lung Disease study. Abnormal exertional breathlessness was defined as a breathlessness (Borg scale 0-10) intensity rating more than the upper limit of normal at the symptom-limited peak of CPET using normative reference equations. RESULTS: of 79.5% predicted (19.0% predicted); 26% showed abnormally low exercise capacity (peak oxygen uptake less than the lower limit of normal). Abnormally high exertional breathlessness was present in 24%, including 9% and 11% of people with mMRC score of 0 and CAT score of < 10, respectively. An mMRC score of ≥ 2 and CAT score of ≥ 10…

BACKGROUND: An increasing number of patients with pulmonary arterial hypertension (PAH) have cardiovascular comorbidities. However, the effects of comorbidities on responses to PAH treatment are not well understood. RESEARCH QUESTION: Do cardiovascular comorbidities in patients with PAH influence the efficacy and tolerability of inhaled or oral treprostinil? STUDY DESIGN AND METHODS: All patients from phase 3 studies Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension (TRIUMPH) (N = 235) and Phase III Clinical Worsening Study of UT-15C in Subjects With PAH Receiving Background Oral Monotherapy (FREEDOM-EV) (N = 690) were included in this post hoc analysis and were classified as having 0, ≥ 1, or ≥ 2 cardiovascular comorbidities of interest based on patient medical history. The mean difference in 6-minute walk distance and N-terminal pro-brain natriuretic peptide from baseline to week 12 was assessed for TRIUMPH, and the risk and incidence of clinical worsening was assessed for patients in FREEDOM-EV. Adverse events were…

The integration of nurse practitioners (NPs) and physician assistants (PAs) into the medical ICU (MICU) is becoming increasingly vital due to the rising number of critically ill patients and the shortage of board-certified intensivists. Successful recruitment and utilization of NPs and PAs in the MICU setting require a unique understanding of potential variations of the scope of practice based on state law and educational backgrounds, as well as the implementation of best practices around training and leadership support. The purpose of this article was to review the best strategies for creating a MICU team with NPs and PAs. Key strategies for identifying suitable NP and PA candidates include assessing their education, certification, licensure, and clinical experience, particularly in critical care settings. It is important for organizations to have structured orientation programs, which should define roles, establish clear reporting structures, and provide competency-based training to ensure effective team integration. Simulation-based training and professional mentoring are…