What is this summary about?This summary describes the results of a clinical study called MANDALA that was published in the New England Journal of Medicine in 2022. In the MANDALA study, researchers looked at a new asthma rescue inhaler that contains both albuterol and budesonide in a single inhaler (known as albuterol-budesonide, AIRSUPRA™). This summary describes the results for people aged 18 yearsand older who took part in the study.
Background: A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still unclear whether this reduction reflects a diminished microbiological burden.
Objectives: The aim of this study was to determine the impact of lumacaftor/ivacaftor on the bacterial and fungal burden.
Design: The study is a prospective multicenter cohort study including 132 CF patients homozygous for F508del treated with lumacaftor/ivacaftor.
Methods: Clinical parameters as well as bacterial and fungal outcomes 1 year after initiation of lumacaftor/ivacaftor were compared to data from 2 years prior to initiation of the treatment. Changes in the slope of the outcomes before and after the onset of treatment were assessed.
Results: Lung function measured as ppFEV1 (p < 0.001), body mass index (BMI) in adults (p < 0.001), and BMI z-score in children (p = 0.007) were improved after initiation of lumacaftor/ivacaftor. In addition, the slope of the prevalence of Streptococcus pneumoniae (p = 0.007) and Stenotrophomonas maltophilia (p < 0.001) shifted from positive to negative, that is, became less prevalent, 1 year after treatment, while the slope for Candida albicans (p = 0.009), Penicillium spp (p = 0.026), and Scedosporium apiospermum (p < 0.001) shifted from negative to positive.
Conclusion: The current study showed a significant improvement in clinical parameters and a reduction of some of CF respiratory microorganisms 1 year after starting with lumacaftor/ivacaftor. However, no significant changes were observed for Pseudomonas aeruginosa, Staphylococcus aureus, or Aspergillus fumigatus, key pathogens in the CF context.
Intracavitary pulmonary aspergilloma is a persistent and life-threatening infection that carries a mortality rate of up to 15%. It occurs when Aspergillus species gain entry to an existing lung cavity. In the absence of definitive treatment, patients may succumb to severe complications such as massive hemoptysis, cachexia, or secondary infections. Aspergillomas often show limited response to antifungal medications, mainly due to insufficient drug concentrations within the cavities. Surgery is frequently the preferred treatment option, but it poses significant risks, and many individuals are ineligible due to underlying health issues. We present the most extensive non-surgical fungal ball cohort to date, managed using an innovative multimodal strategy that combines antifungal therapy before and after bronchoscopic debulking. This was a cross-sectional observational study. For those who cannot undergo surgery, our medical center has pioneered a multimodal approach to aspergilloma resection. This approach combines bronchoscopic endoscopy with antifungal therapy and has been applied successfully to more than 18 patients that are presented in this series. The median age of the cohort was 58 years (range: 32-73), with an equal sex distribution. The mean percent predicted FEV1 was 65.3%. The mean follow-up duration was 3.6 years (range: 0.5-10 years). The cohort receiving antifungals systematically prior to debridement showed a reduction of the pre-existing cavity (40.38 mm versus 34.02 mm, p = 0.021). Across the 18 patients during the follow-up period, 94% remained recurrence-free (defined by symptoms and radiology). Our study fills a critical knowledge gap regarding the significance of initiating antifungal treatment before bronchoscopic debulking and presents a viable approach in these cases for which there is a current unmet therapeutic need.
Background: Lymphangioleiomyomatosis (LAM) is a rare multisystemic disorder characterized by the proliferation of abnormal smooth muscle-like cells. Although serum vascular endothelial growth factor-D (VEGF-D) is currently used as a diagnostic biomarker for LAM, its diagnostic value in Korean patients is unclear.
Objectives: To evaluate the diagnostic value of serum VEGF-D for LAM in Korean patients.
Design: A multicenter prospective cohort study.
Methods: Serum samples were prospectively collected from five medical institutions, from patients with LAM (n = 40) and controls (n = 24; healthy participants = 3, other cystic lung diseases = 13, idiopathic pulmonary fibrosis = 4, idiopathic nonspecific interstitial pneumonia = 4). Serum VEGF-D levels were measured using the enzyme-linked immunosorbent assay, and the diagnostic value was evaluated using receiver operating characteristic (ROC) curve analysis.
Results: The mean age of patients with LAM was 44.5 years, and all were female (controls: 47.8 years; female: 70.8%, p < 0.001). The serum VEGF-D levels were significantly higher in patients with LAM than those in the control group (median: 708.9 pg/mL vs 325.3 pg/mL, p < 0.001). In the ROC curve analysis, serum VEGF-D levels showed good predicting performance for LAM diagnosis (area under the curve = 0.918) with an optimal cut-off value of 432.7 pg/mL (sensitivity = 85.0%, specificity = 87.5%). When 800 pg/mL was used as the cut-off value, the specificity of serum VEGF-D for LAM diagnosis increased to 100.0%.
Conclusion: Our results suggest that serum VEGF-D may be a useful biomarker for diagnosing LAM in Korean patients, similar to previous reports.
Background: Patients with mediastinal lymph node enlargement (MLNE) are diagnosed depending on lymph node biopsy. Whereas, how to obtain larger tissue masses from mediastinal lymph nodes and improve the diagnostic yield of the disease remains to be investigated.
Objectives: Aiming to assess the diagnostic value of endobronchial ultrasound-guided intranodal forceps biopsy via transbronchial laser photoablation (EBUS-IFB-TLP) in patients with MLNE.
Design: A prospective, self-controlled study.
Methods: This study was conducted on 67 MLNE patients requiring a lymph node biopsy for diagnosis at the Henan Provincial People's Hospital and the Fuwai Central China Cardiovascular Hospital in China, from January 2020 to December 2022. Each patient underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA group) and EBUS-IFB-TLP (EBUS-IFB-TLP group) on the same mediastinal lymph node for biopsies. The operation time, diagnostic efficiency, and complication rates of the two biopsy methods were compared.
Results: The number of diagnosed patients in the EBUS-IFB-TLP and the EBUS-TBNA groups was 65 (97.0%) and 57 (85.1%), respectively (p = 0.021). In the EBUS-IFB-TLP group, 28 cases (96.6%) were diagnosed with lung cancer and were classified into different epithelial types. In the EBUS-TBNA group, there were 27 cases (93.1%) diagnosed with lung cancer, of which 26 (89.7%) were classified into different epithelial types. There were 37 (97.4%) and 30 (78.9%) non-lung cancer patients diagnosed in the EBUS-IFB-TLP and EBUS-TBNA groups, respectively (p = 0.039), while 27 cases (96.4%) of sarcoidosis in the EBUS-IFB-TLP group and 20 cases (71.4%) of sarcoidosis in the EBUS-TBNA group were diagnosed (p = 0.016). The percentages of intraoperative mild to moderate bleeding complications were 23.9% (16/67) and 14.9% (10/67) in the EBUS-IFB-TLP and in the EBUS-TBNA groups, respectively (p = 0.109).
Conclusion: This study demonstrated that EBUS-IFB-TLP could be a feasible and effective method in the diagnosis of patients with MLNE, presenting an analogous safety profile compared with EBUS-TBNA. Further studies are needed to verify the diagnostic performance of EBUS-IFB-TLP for MLNE.
Background: Chronic airway obstruction (CAO) and restrictive spirometry pattern (RSP) are associated with mortality, but sex-specific patterns of all-cause and specific causes of death have hardly been evaluated.
Objectives: To study the possible sex-dependent differences of all-cause mortality and patterns of cause-specific mortality among men and women with CAO and RSP, respectively, to that of normal lung function (NLF).
Design: Population-based prospective cohort study.
Methods: Individuals with CAO [FEV1/vital capacity (VC) < 0.70], RSP [FEV1/VC ⩾ 0.70 and forced vital capacity (FVC) < 80% predicted] and NLF (FEV1/VC ⩾ 0.70 and FVC ⩾ 80% predicted) were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-2004. Mortality data were collected through April 2016, totally covering 19,000 patient-years. Cox regression and Fine-Gray regression accounting for competing risks were utilized to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, body mass index, sex, smoking habits and pack-years.
Results: The adjusted hazard for all-cause mortality was higher in CAO and RSP than in NLF (HR, 95% CI; 1.69, 1.31-2.02 and 1.24, 1.06-1.71), and the higher hazards were driven by males. CAO had a higher hazard of respiratory and cardiovascular death than NLF (2.68, 1.05-6.82 and 1.40, 1.04-1.90). The hazard of respiratory death was significant in women (3.41, 1.05-11.07) while the hazard of cardiovascular death was significant in men (1.49, 1.01-2.22). In RSP, the higher hazard for respiratory death remained after adjustment (2.68, 1.05-6.82) but not for cardiovascular death (1.11, 0.74-1.66), with a similar pattern in both sexes.
Conclusion: The higher hazard for all-cause mortality in CAO and RSP than in NLF was male driven. CAO was associated with respiratory death in women and cardiovascular death in men, while RSP is associated with respiratory death, similarly in both sexes.
Background: The adverse effects of pulmonary arterial hypertension (PAH) on physical, emotional, and health-related quality of life (HRQoL) remain primarily unrecognized, especially in resource-limited settings.
Objectives: This study aims to characterize the HRQoL of patients with PAH in this area and also identify the potential role of clinically relevant characteristics, including the 6-min walk distance test (6MWD), WHO-Functional Classification (WHO-FC), and mental health in the occurrence of lowering quality of life.
Design: This was a cross-sectional observational study.
Methods: Inpatients with PAH were chosen from a tertiary hospital located in Gansu province, China. All participants were interviewed face-by-face by using questionnaires, including items from the 36-Item Short Form Health Survey (SF-36), the self-rating anxiety scale, and the self-rating depression scale. Data on demographic and clinically relevant characteristics, including WHO-FC and 6MWD, were also collected by tracing medical recorders. Multiple linear regression analysis was used to determine the association between demographic, clinically relevant characteristics data, and physical component summary (PCS) or mental component summary (MCS) in SF-36.
Results: Of the 152 participants, SF-36 differed significantly from Chinese norms in all eight domains, with role-physical (21.55 ± 9.87) less than one-third of the norm (88.79 ± 28.49). Multiple linear regression results showed that the factors with the greatest impact on PCS were anxiety scores (β = -0.22, p = 0.001), followed by WHO-FC (β = -0.16, p = 0.014) and 6MWD (β = 0.15, p = 0.036). The factors with the greatest impact on MCS were WHO-FC (β = -0.30, p < 0.001), followed by anxiety (β = -0.23, p = 0.001) and depression scores (β = -0.16, p = 0.013).
Conclusion: HRQoL was substantially reduced among PAH patients in the resource-limited area, mainly the physiological functions. WHO-FC and anxiety scores were independently associated with both PCS and MCS in SF-36. Clinicians should make reasonable rehabilitation programs and plans for patients according to their cardiac function grade and the severity of clinical symptoms. In addition, psychological interventions should also be taken, especially for those with anxiety symptoms, so as to improve their HRQoL.
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Faster lung function impairment occurs earlier in the disease, particularly in mild-to-moderate COPD, highlighting the need for early and effective targeted interventions. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024 report recommends initial pharmacologic treatment with a long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) combination in group B (0 or 1 moderate exacerbation not leading to hospitalization, modified Medical Research Council score of ⩾2, and COPD Assessment Test™ score of ⩾10) and E (⩾2 moderate exacerbations or ⩾1 exacerbation leading to hospitalization and blood eosinophil count <300 cells/µL) patients. In randomized controlled trials (RCTs), LAMA/LABA combination therapy improved lung function, St. George's Respiratory Questionnaire (SGRQ) total score, and Transitional Dyspnea Index (TDI) focal score and reduced the use of rescue medications, exacerbation risk, and risk of first clinically important deterioration (CID), compared with LAMA or LABA monotherapy. However, there is limited evidence regarding the efficacy and safety of LAMA/LABA combination therapy versus LAMA or LABA monotherapy in maintenance therapy-naïve patients. This review discusses the rationale for the early initiation of LAMA/LABA combination therapy in maintenance therapy-naïve patients with COPD. In post hoc analyses of pooled data from RCTs, compared with LAMA or LABA monotherapy, LAMA/LABA combination therapy improved lung function and quality of life and reduced COPD symptoms, risk of first moderate/severe exacerbation, risk of first CID, and use of rescue medication, with no new safety signals. In a real-world study, patients initiating LAMA/LABA had significantly reduced risk of COPD-related inpatient admissions and rate of on-treatment COPD-related inpatient admissions over 12 months than those initiating LAMA. Consequently, LAMA/LABA combination therapy could be considered the treatment of choice in maintenance therapy-naïve patients with COPD, as recommended by the GOLD 2024 report.
Background: Chronic obstructive pulmonary disease (COPD) is associated with airflow limitation resulting from a combination of small airway disease (SAD) and parenchymal destruction. Although various diagnostic methods for SAD exist, access to these tools can be limited.
Objectives: This study aimed to explore the correlation between handgrip strength (HGS) and SAD in COPD patients.
Design: Cross-sectional prospective study.
Methods: HGS was measured using a hand dynamometer. SAD was evaluated using impulse oscillometry, with results reported as the difference between respiratory resistance at 5 and 20 Hz (R5-R20). SAD was defined as R5-R20 ⩾0.07 kPa/L/s. The receiver operator characteristic (ROC) curves, sensitivity, and specificity values were calculated to determine the optimal cutoff value of HGS for predicting SAD.
Results: Sixty-four patients (90.6% male) were included. The average age was 72.1 ± 8.3 years, and body mass index was 23.4 ± 4.2 kg/m2. FEV1 was 71.6 ± 21.3%, and HGS was 30.2 ± 8.1 kg. R5-R20 was 0.11 ± 0.08 kPa/L/s. SAD was found in 64.1% of patients. A negative correlation between HGS and R5-R20 was observed (r = -0.332, p = 0.007). The best cutoff value for HGS in detecting SAD was determined to be 28.25 kg, with a sensitivity of 73.9%, specificity of 65.9%, and an area under ROC curve of 0.685 (95% CI 0.550-0.819, p = 0.015).
Conclusion: SAD is common in COPD patients, and HGS is significantly negatively correlated with SAD. This tool might serve as an alternative or adjunctive assessment for small airway dysfunction in COPD patients.
Registration: This study was registered with ClinicalTrials.gov with number NCT06223139.
Background: The preoperative determination of visceral pleural invasion (VPI) in patients with malignant solitary pulmonary nodules (SPNs) is essential for determining the surgical range and selecting adjuvant chemotherapy.
Objectives: This study aimed to systematically investigate risk factors of VPI in patients with SPN and construct a preoperative predictive model for such patients.
Design: This is a retrospective study. The clinical, radiological, and pathological characteristics of study subjects were reviewed, and the groups with and without VPI were compared.
Methods: Multivariate logistic analysis was utilized to identify independent risk factors for VPI. Moreover, a predictive nomogram was constructed to assess the likelihood of VPI occurrence.
Results: Of the 364 enrolled cases, SPNs adjacent to the pleura with VPI were found in 110 (30.2%) patients. By incorporating four preoperative variables, including tumor diameter (>2 cm), maximum computed tomography value (>200 Hu), air bronchogram sign, and age, a preoperative predictive nomogram was constructed. The nomogram demonstrated good discriminative ability, with a C-index of 0.736 (95% CI (0.662-0.790)). Furthermore, our data indicated that the air bronchogram sign (odd ratio (OR) 1.81, 95% CI (0.99-3.89), p = 0.048), a maximum diameter >2 cm (OR 24.48, 95% CI (8.43-71.07), p < 0.001), pathological type (OR 5.01, 95% CI (2.61-9.64), p < 0.001), and Ki-67 >30% (OR 2.95, 95% CI (1.40-6.21), p = 0.004) were overall independent risk factors for VPI.
Conclusion: This study investigated the risk factors for VPI in malignant SPNs touching the pleural surface. Additionally, a nomogram was developed to predict the likelihood of VPI in such patients, facilitating informed decision-making regarding surgical approaches and treatment protocols.
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