Therapeutic Advances in Respiratory Disease最新文献

Background: Benralizumab is a monoclonal antibody treatment for severe eosinophilic asthma (SEA). Few studies investigated its role in airway inflammation and its correlation with lung function.

Objectives: The aim of the present study is to assess its effect after 1 year of treatment, focusing on airway inflammation.

Design: This is a retrospective observational study, in an Italian tertiary reference centre specialised in diagnosis and management of severe asthma patients.

Methods: We conducted a monocentric retrospective study including SEA patients treated with benralizumab for 1 year. Clinical, functional and inflammatory data were collected at baseline, 6 (T6) and 12 (T12) months.

Results: Twenty-two SEA patients on benralizumab were included. We observed a reduction in exacerbations rate and systemic steroid treatment (p < 0.0001) as well as an improvement in asthma control (p < 0.0001), health-related quality of life (p = 0.017) and lung function pre-BD FEV1 (L) (p = 0.02) and percentage (p = 0.004) and post-BD FEV1 (L) (p = 0.01) and percentage (p = 0.003) from baseline to T6 and T12. A reduction in sputum eosinophil percentage was observed at T6 and T12 (p < 0.005). We found a positive correlation between the variation of sputum eosinophils percentage and FEV1 (L) at T12 (rho = -0.79, p = 0.04). Moreover, the improvement of FEF_25%-75% from baseline to 6 (rho = -0.53, p = 0.03) and 12 (rho = -0.62, p = 0.01) months negatively correlated with the duration of asthma disease.In our cohort 12/22 patients were super-responders at T6 and 15/22 at T12. Furthermore, clinical remission was reached by 12/22, and all of them obtained blood and sputum eosinophils counts normalisation.

Conclusion: Our data confirm that it is a rapid and effective treatment for SEA acting on clinical, functional, systemic and airway inflammatory outcomes. Our results highlight the role of induced sputum as a promising non-invasive technique to investigate pathophysiologic mechanisms in severe asthma treated with biologics. Finally, a negative correlation between small airway improvement and the duration of asthma may suggest that a prompt referral to asthma centres may delay lung function worsening. Additional studies are needed to investigate more in-depth the role of induced sputum in the management of asthma, response to treatment and remission.

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: 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.

Background: Maintaining the patient awake and not intubated during the venovenous extracorporeal membrane oxygenation (VV ECMO) reduces the risk of ventilation-induced lung injury in patients with ARDS. Currently, there is a lack of data on outcomes and complications associated with the awake ECMO approach.

Objectives: To evaluate outcomes and the occurrence of complications of awake ECMO approach guided by local safety protocol comprising ultrasound-guided cannulation, argatroban-based anticoagulation, respiratory support, and routine sedation targeted to reduce respiratory effort and keeping nurse-to-patient ratio of 1:1.

Design: A single-center retrospective case series analysis.

Methods: Consecutive patients with COVID-19-related acute respiratory distress syndrome (ARDS) (CARDS) treated by full awake VV ECMO approach from April 2019 to December 2023 were eligible.

Results: Our center treated 10 patients (mean age 54.7 ± 11.6 years) with CARDS with an awake ECMO approach. The reasons for awake ECMO included the presence of barotrauma in six patients, a team consensus to prefer awake ECMO instead of mechanical ventilation in three patients, and the patient's refusal to be intubated in one case. Before ECMO, patients were severely hypoxemic, with a mean value of Horowitz index of 48.9 ± 9.1 mmHg and a mean respiratory rate of 28.8 ± 7.3 breaths per minute on high-flow nasal cannula or noninvasive ventilation support. The mean duration of awake VV ECMO was 558.0 ± 173.6 h. Seven patients (70%) were successfully disconnected from ECMO and fully recovered. Intubation from respiratory causes was needed in three patients (30%), all of whom died eventually. In total, three episodes of delirium, two episodes of significant bleeding, one pneumothorax requiring chest tube insertion, and one oxygenator acute exchange occurred throughout the 5580 h of awake ECMO. No complications related to cannula displacement or malposition occurred.

Conclusion: The awake ECMO strategy guided by safety protocol appears to be a safe approach in conscious, severely hypoxemic, non-intubated patients with COVID-19-related ARDS.

Background: Gastro-esophageal reflux disease (GERD) is a chronic disease that coexists with asthma and is often responsible for repeated exacerbations, as well as has a negative impact on the quality of life (QoL). However, from our continent, there is limited data available on the exact prevalence of GERD in asthma and its association with asthma control and QoL.

Objective: To determine the prevalence of GERD in asthma and see its association with asthma control and QoL.

Design: A prospective, cross-sectional study was conducted over 8 months from September 2020 to April 2021.

Methods: Patients with a confirmed diagnosis of asthma aged 18 years and above were recruited from the outpatient department of pulmonology. Patients' GERD score was calculated using the FSSG SCALE (Frequency Scale for Symptoms of GERD) questionnaire and the Asthma Control Test (ACT) was used to determine asthma control. To assess the QoL, the short form of health survey (SF-36) questionnaire was used. Patients were recruited through a convenience sampling technique.

Results: A total of 190 patients were enrolled, the mean age was 33.7 ± 13.3 years and 55.8% were female. Prevalence of GERD was (136) 71.6%. According to the ACT score, 81 (42.6%) patients had very poorly controlled asthma (mean GERD score of 13.73 ± 7.66), compared to 59 (31.1%) asthmatic patients who had well-controlled asthma (mean GERD score of 11.97 ± 7.39, p = 0.43). SF-36 questionnaire was used to measure QoL showed GERD patients had statistically lower scores in the following domains of QoL: "Role Limitations due to Physical Functioning" (37.78 vs 57.44, p = 0.003), "Energy/Fatigue" (47.47 vs 55.07, p = 0.02), and "Bodily Pain" (63.40 vs 72.84, p = 0.01).

Conclusion: This study showed a high prevalence of GERD among asthmatic patients with a negative impact on QoL but did not demonstrate a statistically significant relationship between GERD and asthma control.

Background: The current available diagnostic criteria for gastroesophageal reflux-related chronic cough (GERC) dominated by non-acid reflux is imperfect. The post-reflux swallow-induced peristaltic wave index (PSPWI) is a parameter reflecting esophageal clearance function.

Objectives: This study aims to investigate its diagnostic value for non-acid GERC.

Design: This study sought to compare the diagnostic value of PSPWI in different types of GERC, particularly non-acid GERC, and explore the clinical significance of PSPWI in the diagnosis of non-acid GERC through diagnostic experiments.

Methods: A retrospective analysis was performed based on 223 patients with suspected GERC who underwent multichannel intraluminal impedance-pH monitoring (MII-pH) in the outpatient clinic of our department from August 2016 to June 2021. Their clinical information, laboratory test results, and treatment responses were assessed and the underlying etiologies of chronic cough were categorized. The predictive value of the PSPWI in diagnosing different types of GERC, especially non-acid GERC, was analyzed and compared.

Results: A total of 195 patients with chronic cough who met the inclusion criteria underwent MII-pH monitoring. 143 patients had a definitive diagnosis of GERC, including 98 with acid GERC and 45 with non-acid GERC. The diagnostic value of PSPWI alone was moderate for GERC with an area under the working curve (AUC) 0.760, but poor for non-acid GERC with an AUC of 0.569. However, PSPWI < 39.8% combining with acid exposure time (AET) ⩽ 6.2% demonstrated a moderate diagnostic value for non-acid GERC, with an AUC of 0.722. When PSPWI < 39.8% combined with a non-acid reflux ratio >68.75%, the diagnostic value for non-acid GERC was improved (AUC_ROC = 0.80 versus AUC_ROC = 0.722, p < 0.05), which was significantly superior to non-acid symptom index (AUC_ROC = 0.804 versus AUC_ROC = 0.550, p < 0.05) and non-acid symptom association probability (AUC_ROC = 0.804 versus AUC_ROC = 0.571, p < 0.05).

Conclusion: PSPWI < 39.8% and AET ⩽ 6.2% have demonstrated good diagnostic value for non-acid GERC. The diagnostic value was further improved when combined with non-acid reflux ratio >68.75%.