What's new in pulmonary and critical care medicine

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ASTHMA

Neuropsychiatric events with initiation of montelukast versus long-acting beta-agonist for asthma (April 2025)

Whether leukotriene antagonist administration results in increased neuropsychiatric events (NPEs) in children and adolescents is controversial. Large observational studies often demonstrate an association with increased risk; however, this may be related to worsening asthma control in those who required leukotriene antagonist initiation. In a new national database study from Sweden, investigators compared new montelukast users with new long-acting beta-agonist (LABA) users to help avoid this confounding. Incident neuropsychiatric adverse events were uncommon and nearly identical in those with new montelukast use compared with those with LABA use (2.39 versus 2.41 per 100 patient-years; hazard ratio 0.99) [1]. These data should offer reassurance to clinicians and caregivers of those who require these medications. (See "Antileukotriene agents in the management of asthma", section on 'Leukotriene receptor antagonists'.)

Prevalence of eosinophilic granulomatosis with polyangiitis in patients presenting with severe asthma (March 2025)

Patients presenting with difficult-to-control asthma require careful clinical assessment to determine optimal therapy and rule out other disease processes. This is well illustrated by a recent study of 596 patients presenting with severe asthma, of whom nearly 4 percent were found to have eosinophilic granulomatosis with polyangiitis (EGPA) [2]. Nearly all patients identified with EGPA had a peak blood eosinophil count greater than 1000 cells/microL, and the most frequent additional disease manifestations were upper airway disease, neuropathy, and kidney involvement. Our authors support carefully assessing all severe asthma patients for hypereosinophilia and extrapulmonary disease. (See "Evaluation of severe asthma in adolescents and adults", section on 'Assessing conditions that mimic asthma'.)

Transcriptional profiling of asthma in children and adolescents (January 2025)

Childhood-onset asthma traditionally is thought to be primarily mediated by allergic processes (typically characterized by hypereosinophilia and elevated levels of interleukins 4, 5, and 13). However, a new cross-sectional analysis of nasal epithelial transcription profiles from three studies of predominantly African American and Puerto Rican youths with asthma (aged 6 to 20 years) found that nearly 75 percent of participants did not have an allergic (type 2) gene signature [3]. Instead, these patients had transcriptomic profiles consistent with either Th17-mediated inflammation or a third endotype that included neither type 2 nor Th17-responsive genes. This finding may explain why pediatric asthma may not respond to therapies that target type 2 immune responses and implies that many patients would benefit from treatments that focus on other inflammatory pathways. (See "Characterizing severe asthma phenotypes", section on 'Neutrophilic asthma'.)

Ultra-long-acting asthma biologic therapy (January 2025)

Biologic therapies are highly effective for severe asthma, but routine re-administration can be burdensome. In two simultaneous placebo-controlled trials of an ultra-high affinity antibody targeting interleukin-5 (depemokimab), 792 adolescents or adults with at least two asthma exacerbations in the past year despite medium- or high-dose inhaled glucocorticoids and an elevated blood eosinophil count were randomly assigned to depemokimab (100 mg subcutaneously every six months) or placebo and followed for one year [4]. Patients receiving depemokimab demonstrated a substantial reduction in annualized asthma exacerbations compared with patients receiving placebo (rate ratio 0.46) but no meaningful improvements in daily asthma symptoms or respiratory quality of life. Rates of adverse events were largely similar among the two groups. These favorable results may portend regulatory approval of ultra-long-acting asthma biologics. (See "Treatment of severe asthma in adolescents and adults", section on 'Experimental approaches'.)

Use of anti-inflammatory reliever therapies to reduce asthma exacerbations (November 2024)

Use of inhalers containing both a fast-acting bronchodilator and anti-inflammatory inhaled corticosteroids (ICS) for relief of symptoms has reduced the rate of asthma exacerbations compared with short-acting beta-agonists (SABA) alone in several randomized trials of adolescents and adults. In a new network meta-analysis, compared with SABA alone, severe asthma exacerbations were significantly reduced for both ICS-formoterol (13 trials, 19,184 patients; risk difference 10.3 percent, risk ratio [RR] 0.65) and ICS-SABA (4 trials, 4852 patients; risk difference 4.7 percent, RR 0.84) [5]. Our authors recommend these anti-inflammatory reliever therapies for those with variable asthma symptoms or frequent exacerbations and prefer them for all patients with asthma. (See "Ongoing monitoring and titration of asthma therapies in adolescents and adults", section on 'Anti-inflammatory reliever therapy (AIR) to reduce exacerbations'.)

COPD

Polygenic risk score to identify undiagnosed COPD (January 2025)

Chronic obstructive pulmonary disease (COPD) remains underdiagnosed despite case-finding strategies to actively identify those who have compatible symptoms and clinical risk factors (eg, smoking) and would thus warrant confirmatory spirometry testing. In a study evaluating almost 7500 patients from two cohorts from the United States, adding a polygenic risk score (PRS) to a traditional case-finding questionnaire helped retrospectively identify additional patients with undiagnosed moderate to severe airflow obstruction, particularly among younger patients with lower COPD risk [6]. This study highlights the potential value of incorporating genetic risk to identify patients for spirometry testing. However, whether patients identified by PRS rather than traditional case-finding benefit from early COPD treatment remains unknown, and PRS is not yet routinely used in clinical practice. (See "Chronic obstructive pulmonary disease: Risk factors and risk reduction", section on 'Gene polymorphisms'.)

CRITICAL CARE

Securing central venous catheter dressings (May 2025)

A central venous catheter (CVC) must be secured to the skin to stabilize it, but the optimal dressing is unclear. In a randomized trial of patients undergoing jugular CVC insertion, application of medical liquid adhesive (MLA) under the standard CVC dressing border resulted in fewer dressing failures due to lifting edges at seven days compared with a standard dressing alone (28 versus 50 percent) [7]. Skin complications were similar between the groups. While MLA improved catheter securement and dressing integrity, a larger trial is needed to evaluate clinically important outcomes such as infection, catheter loss, and other complications. (See "Routine care and maintenance of intravenous devices", section on 'Device securement'.)

Inhaled sevoflurane not beneficial in acute respiratory distress syndrome (April 2025)

Preliminary data suggested that the gaseous anesthetic sevoflurane may be efficacious as a sedative in mechanically ventilated patients. However, in a trial of 687 patients with early moderate to severe acute respiratory distress syndrome (ARDS), compared with patients treated with propofol, patients randomized to sevoflurane had fewer ventilator-free days (between-group difference -2.1, 95% CI -3.6 to -0.7) and lower 7- and 90-day survival (90.6 versus 86.5 percent; 47.1 versus 55.7 percent, respectively) [8]. In addition, patients receiving sevoflurane had higher lactate levels, acute kidney injury rates, and sevoflurane-specific adverse effects (eg, arginine vasopressin resistance and malignant hyperthermia). These findings do not support inhaled sevoflurane use as a sedative in patients with ARDS. (See "Sedative-analgesia in ventilated adults: Medication properties, dose regimens, and adverse effects", section on 'Sevoflurane'.)

Duration of antibiotics for gram-negative bacillary bacteremia (April 2025)

Although bacteremia had traditionally been treated with at least 14 days of antibiotics, mounting data indicate that shorter courses are often appropriate. In a randomized trial of over 3600 hospitalized patients with bloodstream infections (mostly due to gram-negative bacilli), 90-day mortality was similar in patients treated with 7 or 14 days of antibiotics (15 versus 16 percent) [9]. Patients with immunocompromising conditions, prosthetic heart valves or vascular grafts, a syndrome requiring prolonged therapy (eg, endocarditis), or Staphylococcus aureus bacteremia were excluded from the study. A recent meta-analysis reported similar findings [10]. These data support our approach to treat most patients with uncomplicated gram-negative bacillary bacteremia with seven days of antibiotics. (See "Gram-negative bacillary bacteremia in adults", section on 'Duration and route of therapy'.)

Coated versus standard peripherally inserted central catheters (April 2025)

Whether specialized materials or coatings reduce complications from peripherally inserted central catheters (PICC) has been uncertain. In a randomized trial including over 1000 patients, those assigned to receive a chlorhexidine PICC had a higher complication rate than those assigned to a hydrophobic or standard polyurethane PICC (approximately 39, 22, and 22 percent respectively) [11]. The device failure rate was not significantly different among the three groups and was defined as the cessation of PICC function or the need to remove the PICC before completion of the intended therapy. The results of this trial support our practice of using standard PICCs. (See "Central venous access: Device and site selection in adults", section on 'Antimicrobial-impregnated catheters'.).

Outcomes associated with sepsis bundles (April 2025)

A "sepsis bundle" refers to a set of early interventions (eg, intravenous fluids, antibiotics, and laboratory tests) that improve the diagnosis, management, and survival of patients with sepsis; the time required to complete the "sepsis bundle" is widely used in hospitals as a pay-for-performance measure. A recent review analyzed 17 observational trials examining outcomes associated with compliance or implementation of a sepsis bundle [12]. Five studies demonstrated a mortality benefit from bundle compliance while seven did not. Only one study showed a mortality benefit from bundle implementation. High-quality data are needed to demonstrate a clear mortality benefit from sepsis bundles. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Early goal-directed therapy'.)

Procalcitonin and antibiotic duration in sepsis (April 2025)

While procalcitonin (PCT) has a clear role in determining antibiotic duration for patients with community-acquired pneumonia, its role in managing sepsis is less clear. A recent multicenter randomized trial of 2760 adults with sepsis, reported a reduction in antibiotic duration for patients in whom a daily PCT-guided protocol was implemented compared with standard care (9.8 versus 10.7 days) [13]. However, over half of study participants had lower respiratory tract infections which may have impacted the outcome. Based upon these and other cumulating data in patients with sepsis, we support measuring PCT to guide antibiotic duration. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Initial investigations'.)

Society of Critical Care Medicine guidelines on critical care ultrasonography use (March 2025)

The Society of Critical Care Medicine (SCCM) recently updated its guidelines on the use of bedside critical care ultrasonography (CCUS) [14]. The SCCM conditionally recommended CCUS use in patients with septic shock, acute respiratory failure, and acute cardiogenic shock as well as in patients with unclear volume status. It was unable to make a clear recommendation for CCUS use in patients undergoing cardiopulmonary resuscitation. We agree with these recommendations. (See "Indications for bedside ultrasonography in the critically ill adult patient", section on 'Introduction'.)

Society of Critical Care Medicine guidelines for family/caregivers in the intensive care unit (March 2025)

The Society of Critical Care Medicine (SCCM) issued updated guidelines on family/caregiver support in the intensive care unit (ICU) [15]. Using a growing body of evidence, the SCCM issued a strong recommendation for liberal caregiver/family presence in the ICU. This includes family/caregiver presence on rounds and resuscitation, participation in care as well as the provision of dedicated space, ICU diaries, education tools, and psychological, spiritual, and bereavement support. The SCCM also made a conditional recommendation for communication support for both family/caregivers and clinicians. We agree with the recommendations. (See "Post-intensive care syndrome (PICS): Treatment and prognosis", section on 'Post-intensive care syndrome-family'.)

Thymosin alpha 1 not beneficial in sepsis (February 2025)

Preliminary data suggest that thymosin-alpha 1, an agent that enhances the effect of T helper 1 cells, may be beneficial in patients with sepsis. However, a phase 3 randomized trial of subcutaneous thymosin alpha 1 for seven days in 552 patients with sepsis reported similar 28-day mortality when compared with 554 patients treated with placebo [16]. Other outcomes (including 90-day mortality, new onset infection rates, and microorganism clearance rates) were also similar. Although the drug may have been underdosed and the study underpowered to detect a mortality difference, these results are not encouraging for further trials of this agent in sepsis. (See "Investigational and ineffective pharmacologic therapies for sepsis", section on 'Immunostimulation'.)

Inappropriate use of plasma in the intensive care unit (January 2025)

Plasma is thought to be over-used, often without a compelling indication. A new multicenter study supports this impression and illustrates the magnitude of misuse [17]. Among 3643 individuals in the intensive care unit (ICU), 10 percent received one or more plasma transfusions; of these, 37 percent did not have a strong indication and might have been avoided, such as mild elevations of the international normalized ratio (INR) in nonbleeding patients. Plasma transfusion should be limited to situations with a strong clinical rationale and/or demonstrated efficacy. (See "Use of blood products in the critically ill", section on 'Plasma indications'.)

Safety of antithrombotic therapy in factor XI deficiency (January 2025)

Spontaneous bleeding is rare in factor XI deficiency, suggesting that anticoagulation or antiplatelet therapy may be safer in these individuals than in those with other bleeding disorders. A new database study evaluated bleeding risk in approximately 50 percent of the general population in Israel [18]. While use of an anticoagulant or antiplatelet agent increased bleeding risk, individuals with factor XI deficiency did not have an appreciably higher rate of bleeding with these treatments than individuals without factor XI deficiency. These results suggest that antithrombotic therapy may be used when needed in individuals with factor XI deficiency, using shared decision-making based on the individual's bleeding phenotype and thrombotic risk. (See "Factor XI (eleven) deficiency", section on 'Anticoagulation or antiplatelet therapy'.)

Advanced respiratory support in COVID-19 (January 2025)

In patients with COVID-19 who need advanced respiratory support, choosing between high-flow oxygen delivered via nasal cannulae (HFNC) and noninvasive ventilatory (NIV) support is challenging. In a recent trial of 1800 patients with acute respiratory failure from COVID-19 randomized to HFNC versus NIV, similar rates of endotracheal intubation (approximately 30 percent) and death (12 percent) were reported at the end of one week [19]. Subgroup analyses were not helpful in modality selection. In patients with COVID-19 who need advanced respiratory support, we use the patient's comorbidities and the tolerability of the device to help choose between NIV and HFNC. (See "COVID-19: Respiratory care of the nonintubated hypoxemic adult (supplemental oxygen, noninvasive ventilation, and intubation)", section on 'Choosing oxygen via high-flow nasal cannulae versus noninvasive ventilation'.)

Electronic alert systems for sepsis (January 2025)

Increasingly, hospitals are automatically screening patients for evidence of sepsis, but the effectiveness of this approach is unclear. In a recent cluster randomized trial of an electronic medical record (EMR) sepsis screening alert system in 5 hospitals and over 60,000 patients, adjusted 90-day mortality was lower in patients who were electronically screened (adjusted relative risk 0.85; 95% CI, 0.77-0.93) [20]. Screening reduced vasopressor therapy administration and new multidrug-resistant organisms but increased kidney replacement therapy and new C difficile (colonization or infection unknown). Automated EMR alerts for sepsis may impact provider behavior and patient outcomes; however, which factors should be used for screening, and the best way to alert providers to this information, require further study. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis", section on 'Identification of early sepsis (qSOFA, NEWS)'.)

Point-of-care-ultrasound in patients with shock (January 2025)

Point-of-care-ultrasound (POCUS) is increasingly being used in patients with shock to assess etiology and monitor treatment response. A recent meta-analysis of 18 randomized trials in patients with shock found that POCUS-guided resuscitation reduced the duration of vasoactive medication (mean difference -0.73 days), and may reduce 28-day mortality and the need for kidney replacement therapy (relative risk 0.88 and 0.80, respectively; borderline statistical significance) [21]. The use of POCUS did not impact the administration of fluids or inotropes, length of stay, or need for mechanical ventilation. We continue to encourage the use of POCUS when managing patients with shock of unclear etiology. (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock", section on 'Point-of-care ultrasonography'.)

Uncertain role of systemic antibiotics to prevent ventilator-associated pneumonia (December 2024)

Ventilator-associated pneumonia (VAP) is a significant cause of mortality in patients in the intensive care unit (ICU). In a recent randomized trial of patients with moderate or severe traumatic brain injury (TBI) or acute stroke, ceftriaxone 2 g intravenously (IV) within 12 hours of intubation reduced 7-day VAP rates (14 versus 32 percent) and 28-day mortality rates (15 versus 25 percent) compared with placebo without excess adverse effects [22]. However, in a subsequent meta-analysis including that trial and six others with over 800 patients with acute brain injury (stroke, TBI, or post-cardiac arrest), a short course of peri-intubation IV antibiotics reduced the incidence of VAP, but significant differences in the number of ventilator-free days, ICU length of stay, or in-hospital mortality were not detected [23]. Given the uncertainty around these effects, practice among UpToDate contributors vary; some do not routinely use systemic antibiotics for prevention of VAP in the ICU because of concern for promoting antibiotic resistance, whereas others suggest a single peri-intubation dose of ceftriaxone to prevent VAP in selected populations at high risk (eg, patients with acute TBI). (See "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Prevention' and "Management of acute moderate and severe traumatic brain injury", section on 'Mechanical ventilation'.)

Intensity level of noninvasive ventilation in acute exacerbation of COPD (December 2024)

In patients with acute hypercapnia due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD), bilevel noninvasive ventilation (NIV) reduces mortality and intubation rates, but the ideal level of pressure support is uncertain. In a recent randomized trial of patients with AECOPD who tolerated an initial six hours of low-intensity NIV, patients assigned to receive continued low-intensity NIV (peak inspiratory airway pressure [IPAP] <20 cm H₂O) were more likely to meet criteria for intubation compared with those assigned to high-intensity NIV (peak IPAP 20 to 30 cm H₂O; 13.7 versus 4.8 percent, respectively) [24]. However, the rates of actual intubation were similar in both groups. Crossover from the low- to the high-intensity group may have prevented intubation but complicates interpretation of the study. In addition, the study was stopped early for benefit and underpowered for any mortality difference. Until more data are available, we continue to initiate bilevel NIV at low levels and increase as needed to relieve respiratory distress or improve ventilation. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Acute exacerbation of chronic obstructive pulmonary disease with hypercapnic respiratory acidosis'.)

Optimal screening frequency and breathing trial technique for extubation readiness (December 2024)

Once-daily extubation readiness screening followed by pressure support ventilation spontaneous breathing trials (PSV-SBTs) is typically used to liberate patients off mechanical ventilation. However, some experts screen more frequently or use-T-piece SBTs. In a recent randomized trial, time to extubation was shorter in those who underwent once-daily screening and PSV-SBT compared with once-daily screening and T-piece SBT (2 versus 3.1 days) [25]. Unexpectedly, more frequent screening lengthened the time to extubation, especially in those undergoing PSV-SBT compared with T-piece SBT (3.9 versus 2.9 days). We consider frequent screening to be investigational and continue to use once-daily screening with PSV-SBT as our initial ventilator liberation strategy. (See "Initial weaning strategy in mechanically ventilated adults", section on 'Choosing ventilatory support'.)

Video laryngoscopy during intubation in critically ill patients (October 2024)

In a new meta-analysis with 20 trials and over 4000 emergency department and intensive care unit patients, video laryngoscopy (VL) increased first-pass success during endotracheal intubation compared with direct laryngoscopy (DL; 82 versus 72 percent) [26]. These findings are consistent with a previous meta-analysis and support our recommendation to use VL, if available, instead of DL during emergency intubation. (See "Overview of advanced airway management in adults for emergency medicine and critical care", section on 'Choice of laryngoscopy technique'.)

INTERVENTIONAL PULMONOLOGY

Endobronchial valves for prolonged air leak in high-risk patients (December 2024)

The role of bronchoscopic endobronchial valve (EBV) therapy for prolonged air leak (PAL) in high-risk patients who are unresponsive to conservative therapy (thoracostomy with or without suction) is unknown. In a recent review of 66 high-risk surgical candidates in whom a PAL was present for a median of 24 days, the air leak resolved in 60 percent of patients within 30 days of EBV placement [27]. There were no procedure-related deaths, and the complication rate was 6 percent. This study suggests that EBV placement may be an option in high-risk patients with PAL who are not surgical candidates. However, given the retrospective nature of the study, it is unknown if PAL resolution would have occurred with continued conservative therapy. (See "Alveolopleural fistula and prolonged air leak in adults", section on 'Bronchoscopic interventions'.)

LUNG CANCER

Tumor, Node, Metastasis staging for thoracic cancers (ninth version) (February 2025, Modified March 2025)

The American Joint Commission on Cancer has revised the Tumor, Node, Metastasis (TNM) staging system for a number of cancers [28]. Notable revisions for thoracic cancers include changes to nodal staging in lung cancer (table 1), such that there is now a division of N2 disease into N2a (tumor involvement of a single ipsilateral mediastinal nodal station or of the subcarinal nodal station) and N2b (tumor involvement of multiple ipsilateral mediastinal nodal stations). Revisions have also been made in the staging of pleural mesothelioma (table 2) as well as thymic tumors (table 3). (See "Clinical presentation, diagnosis, and staging of thymoma and thymic carcinoma", section on 'Staging system' and "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer", section on 'Staging'.)

American College of Chest Physicians guidelines on management of central airway obstruction (February 2025)

The American College of Chest Physicians has published its first consensus guideline on the management of central airway obstruction [29]. It promotes the use of therapeutic rigid (rather than flexible) bronchoscopy, general anesthesia, and local ablative therapies to achieve immediate airway patency. The guideline recommends airway dilation in patients undergoing therapeutic bronchoscopy who have stenotic, nonmalignant central airway obstruction, and stent placement for patients with symptomatic malignant or nonmalignant central airway obstruction, after other modalities have failed. The guideline also recommends curative surgical resection, when feasible. We agree with these recommendations. (See "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults" and "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Introduction'.)

Nonsurgical biopsy modalities for peripheral pulmonary nodules (December 2024)

The optimal non-open surgical biopsy modality for peripheral pulmonary nodules (PPNs) is unclear. One recent network meta-analysis reported that computed tomography (CT)-guided transbronchial needle aspiration (CT-TBNA) had the highest diagnostic yield (89 percent), followed by robot-assisted bronchoscopy (RAB; 85 percent) and radial endobronchial ultrasound (rEBUS; 72 percent) [30]. However, CT-TBNA had the highest rate of pneumothorax requiring chest tube drainage (1.6 percent versus <1 percent for RAB or rEBUS) and bleeding (5.2 percent versus <1.5 percent RAB or rEBUS). This study summarizes two important factors that we take into consideration when choosing a non-open surgical biopsy modality for PPNs. Additional factors include PPN location and local expertise. (See "Image-guided bronchoscopy for biopsy of peripheral pulmonary lesions", section on 'Image-guided bronchoscopy techniques'.)

LUNG TRANSPLANTATION

Risk factors for and characteristics of patients with probable chronic lung allograft dysfunction (February 2025)

Patients with a decline in lung function over ≥3 weeks following lung transplantation are considered to have "probable" chronic lung allograft dysfunction (CLAD); while CLAD is a major cause of morbidity and mortality, patients with "probable CLAD" have not been well characterized. In a new multicenter study of 745 patients following lung transplant, 80 percent of those who were found to have "probable CLAD" on pulmonary function test (PFT) monitoring proceeded to meet criteria for "definite CLAD" [31]. Risk factors for probable and definite CLAD were similar and included cytomegalovirus infection, abnormal lung histology, and late presence of donor-specific alloantibodies. Based on these results, patients with "probable CLAD" should be managed as having new-onset CLAD, without awaiting a definitive diagnosis. (See "Chronic lung allograft dysfunction: Bronchiolitis obliterans syndrome", section on 'Definition' and "Chronic lung allograft dysfunction: Bronchiolitis obliterans syndrome", section on 'Etiology and risk factors'.)

PLEURAL DISEASE

European Respiratory Society guidelines on benign pleural effusion (February 2025)

The European Respiratory Society has published its first consensus guideline on the management of nonmalignant pleural effusion [32]. The guideline emphasizes the moderate specificity of Light's criteria for distinguishing exudates from transudates and promotes the use of alternate tests (eg, pleural fluid lactate dehydrogenase, cholesterol); when heart failure (HF) is suspected, they suggest using the serum-effusion albumin gradient and N-terminal pro-brain natriuretic peptide (NT-BNP) levels. The guideline also supports a low threshold for pleural interventions (eg, therapeutic thoracentesis, indwelling catheter) for refractory pleural effusions due to HF, hepatic hydrothorax, and end-stage kidney failure and for biopsy for benign asbestos-related pleural effusions. We agree with these recommendations. (See "Management of nonmalignant pleural effusions in adults", section on 'Introduction' and "Pleural fluid analysis in adults with a pleural effusion".)

CT-guided biopsy and cystic airspaces (January 2025)

Clinicians may hesitate to biopsy cystic lung lesions due to concerns regarding safety or diagnostic yield. However, a retrospective study demonstrated a similar frequency of complications among 90 patients with cystic lung lesions and 180 patients with non-cystic lung lesions who underwent computed tomography (CT)-guided transthoracic needle biopsy (40 versus 38 percent) [33]. Both groups had similar rates of specific complications (eg, hemorrhage, pneumothorax) and similar rates of non-diagnostic biopsies (12 versus 9 percent). These data suggest that CT-guided biopsy is a reasonable option for properly selected patients with cystic lung lesions, bearing in mind that these study findings may be subject to selection bias. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Transthoracic needle biopsy'.)

PULMONARY VASCULAR DISEASE

Sotatercept in severe pulmonary arterial hypertension (April 2025)

Sotatercept, an activin signaling inhibitor, benefits patients with mild to moderate pulmonary arterial hypertension (PAH), but its impact on patients with more severe PAH has been unclear. In a recent randomized trial of 172 patients with severe PAH, subcutaneous sotatercept (0.3 to 0.7 mg per kg every 21 days) added to standard-of-care therapies reduced mortality (8.1 versus 15.1 percent), lung transplantation rates (1.2 versus 7 percent), and hospitalization rates for worsening PAH (9.3 versus 50 percent) [34]. Sotatercept-specific adverse effects included telangiectasias, increased hemoglobin level, thrombocytopenia, epistaxis, and gingival bleeding. Although the study was stopped early (for benefit), these data support a new role for sotatercept as part of a combination therapy regimen in patients with severe PAH. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy", section on 'Combination therapy containing a parenteral agent'.)

Reduced-dose apixaban and rivaroxaban for indefinite venous thromboembolism treatment (April 2025)

The optimal anticoagulant dose for prevention of venous thromboembolism (VTE) among patients at high risk of recurrence is unknown. In a trial of over 2700 such patients who had completed 6 to 24 months of anticoagulation, patients who transitioned either to reduced-dose apixaban (2.5 mg twice daily) or rivaroxaban (10 mg once daily) had a higher five-year VTE recurrence rate, compared with patients who continued to take full-dose anticoagulants (2.2 versus 1.8 percent) [35]. However, low-dose anticoagulant therapy was associated with a lower risk of major and/or clinically relevant bleeding (9.9 versus 15.2 percent). Low-dose apixaban or rivaroxaban is appropriate for most patients at high risk of recurrent VTE who require indefinite anticoagulation. (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation", section on 'Reduced-dose regimens for indefinite anticoagulation'.)

Seventh World Symposium pulmonary hypertension guidelines (January 2025)

Guidelines were issued by the Seventh World Symposium on Pulmonary Hypertension (PH) [36]. These guidelines highlight the importance of fast-track referral to PH centers. comprehensive baseline risk assessment prior to treatment, initial combination therapy (even for mild pulmonary arterial [PAH]), and the inclusion of sotatercept (a new class of medication that inhibits transforming growth factor-beta) to PAH regimens. The new guidelines also replace the term "acute responders at vasoreactivity testing" with "long-term responders to calcium channel blockers (CCB)," since some acute responders still require treatment with PAH-targeted drugs beyond CCB. We agree with these recommendations. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Introduction'.)

Inferior vena cava filter retrieval rates among Medicare beneficiaries (November 2024)

Although retrievable inferior vena cava (IVC) filters should be removed when their protection is no longer needed, removal rates vary widely depending on the population studied. In a review of nearly 271,000 Medicare beneficiaries, the proportion of removed IVC filters increased incrementally after 2014; however, the cumulative incidence of removal was only 17 percent at a maximum follow-up of nine years [37]. This low rate compared with other studies may reflect population characteristics associated with lower removal rates (eg, older age, cancer). Nevertheless, this study underscores the need to periodically reevaluate whether a patient with an IVC filter is a candidate for its removal regardless of age or medical comorbidities. (See "Placement of vena cava filters and their complications", section on 'Filter retrieval'.)

OTHER PULMONARY MEDICINE

Brensocatib therapy for bronchiectasis with frequent exacerbations (April 2025)

Bronchiectasis is the third most common chronic pulmonary disorder in adults, but there are very few evidence-based treatments available. Brensocatib is a new class of therapy designed to target neutrophilic inflammation by inhibiting activation of neutrophil serine proteases. In a phase 3 trial, 1721 patients who had at least two bronchiectasis exacerbations in the prior year were treated with brensocatib 10 mg daily, brensocatib 25 mg daily, or placebo for 52 weeks [38]. Participants receiving brensocatib had a 20 percent decrease in annual exacerbation rates compared with participants receiving placebo. In each treatment group, 48.5 percent of participants remained exacerbation-free during treatment, compared with 40 percent of control participants. Overall, brensocatib was well tolerated; mild to moderate hyperkeratosis was the most frequent drug-specific side effect, occurring in 1.5 to 3 percent of patients. Although the role of brensocatib in relation to traditional antibiotic therapies has yet to be well defined, the prospect of a new therapeutic agent is welcome news for the bronchiectasis community. (See "Bronchiectasis in adults: Treatment of acute and recurrent exacerbations", section on 'Experimental approaches'.)

Lithium aspartate ineffective for neurocognitive effects of long COVID (November 2024)

Anecdotal reports have suggested a benefit from low-dose lithium in patients with neurocognitive symptoms due to long COVID. However, in a placebo-controlled randomized trial in 52 patients with at least four weeks of neurocognitive symptoms following COVID-19 infection, three weeks of lithium aspartate (10 to 15 mg daily) failed to improve fatigue or cognitive dysfunction scores [39]. Limitations included small sample size and possible under-dosing. While low-dose lithium does not appear to benefit patients with long COVID-associated neurocognitive symptoms, further exploratory studies may be warranted. (See "COVID-19: Management of adults with persistent symptoms following acute illness ("long COVID")", section on 'Investigational therapies'.)

High diagnostic uncertainty in community-acquired pneumonia (October 2024)

Because community-acquired pneumonia (CAP) is common and its symptoms overlap with many other cardiopulmonary disorders, it is both over- and underdiagnosed on presentation. In a recent study of over two million hospitalizations in the US Veterans Administration health system, 36 percent of over 215,000 patients with an initial emergency department (ED) diagnosis of pneumonia did not carry this diagnosis upon hospital discharge, and 33 percent of over 239,000 patients discharged with a diagnosis of pneumonia and positive initial chest imaging lacked an ED diagnosis [40]. These findings reinforce the importance of assessing patients initially diagnosed with CAP for alternative processes and being open to the possibility of CAP in patients initially diagnosed with other conditions. (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults", section on 'General approach'.)