Therapeutic Advances in Respiratory Disease最新文献

Background: The presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies in dermatomyositis (DM) is associated with an increased risk of developing rapidly progressive interstitial lung disease (RP-ILD) and a poor prognosis.

Objectives: We aimed to explore whether tofacitinib could improve the prognosis of Anti-MDA5 antibody positive DM-interstitial lung disease (ILD).

Design: Systematic review and meta-analysis.

Data sources and methods: Studies were included if they compared mortality rate and infection events in patients with anti-MDA5 antibody positive DM-associated ILD who were treated with or without tofacitinib.

Results: The systematic review and meta-analysis included a total of 148 patients from four cohort studies. Fifty-eight patients with anti-MDA5 antibody positive DM-ILD who received combined treatment-containing tofacitinib were enrolled in the experimental group. Additionally, 90 DM-ILD patients who did not receive tofacitinib-based therapy were included in the control group. The pooled risk ratio (RR) for all-cause mortality was 0.61 (95% CI, 0.41-0.91, p = 0.02) with I² = 0 indicating no heterogeneity among the included studies. For virus infection risk, the pooled RR was 1.92 (95% CI, 0.90-4.10, p = 0.09), while bacterial and fungal infection-associated RRs were found to be 1.29 (95% CI, 0.65-2.55, p = 0.47) and 1.15 (95% CI, 0.46-2.89, p = 0.77), respectively. There was no statistically significant difference in infection risk between the two groups, and no heterogeneity was observed.

Conclusion: Our findings suggest that tofacitinib may reduce the risk of all-cause mortality in patients with anti-MDA5 antibody-positive DM-ILD without an increased risk of additional infections.

Trial registration: PROSPERO: CRD42023445427; https://www.crd.york.ac.uk/prospero/.

Background: Early diagnosis of malignant pleural effusion (MPE) is of great significance. Current prediction models are not simple enough to be widely used in heavy clinical work.

Objectives: We aimed to develop a simple and efficient clinical prediction scoring system to distinguish MPE from benign pleural effusion (BPE).

Design: This retrospective study involved patients with MPE or BPE who were admitted in West China Hospital from December 2010 to September 2016.

Methods: Patients were divided into training, testing, and validation set. Prediction model was developed from training set and modified to a scoring system. The diagnostic efficacy and clinical benefits of the scoring system were estimated in all three sets.

Results: Finally, 598 cases of MPE and 1094 cases of BPE were included. Serum neuron-specific enolase, serum cytokeratin 19 fragment (CYFRA21-1), pleural carcinoembryonic antigen (CEA), and ratio of pleural CEA to serum CEA were selected to establish the prediction models in training set, which were modified to the scoring system with scores of 6, 8, 10, and 9 points, respectively. Patients with scores >12 points have high MPE risk while ⩽12 points have low MPE risk. The scoring system has a high predictive value and good clinical benefits to differentiate MPE from BPE or lung-specific MPE from BPE.

Conclusion: This study developed a simple clinical prediction scoring system and was proven to have good clinical benefits, and it may help clinicians to separate MPE from BPE.

Background: Cough hypersensitivity is an important part of the neurophysiology of cough, which presents with increased cough response to a lower level of stimuli or triggers. Classification of stimuli might bring about additional insight into the underlying mechanisms and management.

Objectives: This study investigated the profile of cough triggers in chronic cough patients and their relationship with capsaicin cough sensitivity.

Design: This was a cross-sectional observational study.

Methods: We enrolled patients with different causes of chronic cough from 2006 to 2021. Cough triggers were defined as cough response to chemical triggers, mechanical triggers, meal triggers, or thermal trigger. Cough sensitivity to capsaicin was evaluated by the capsaicin challenge test, which was expressed as the lowest concentration of capsaicin inducing 5 or more coughing (C5).

Results: Among 1211 patients with chronic cough, 1107 (91.4%) patients reported at least one cough trigger. Chemical triggers (66.9%) were the most common cough triggers, followed by thermal exposure (50.6%), mechanical triggers (48.2%), and meal triggers (21.2%). There was no difference in the proportion of chemical triggers among different etiologies. Patients with refractory chronic cough reported the highest prevalence of cough triggers (97.1%). A higher number of meal triggers (34.9%) was associated with gastroesophageal reflux-related cough, and meal triggers and mechanical triggers were more common in refractory chronic cough. Among 254 patients who completed capsaicin challenge test, both the number of total triggers and the number of chemical triggers had a significant but mild correlation with capsaicin cough sensitivity.

Conclusion: Cough hypersensitivity as reflected by a variety of cough triggers is a common feature in chronic cough patients, but different etiologies present specific profiles of cough triggers, which could not be evaluated comprehensively by capsaicin cough sensitivity.

Background: The individualized PREdiction of DIsease Control using digital sensor Technology (iPREDICT) program was developed for asthma management using digital technology. Devices were integrated into daily lives of patients to establish a predictive model of asthma control by measuring changes from baseline health status with minimal device burden.

Objectives: To establish baseline disease characteristics of the study participants, detect changes from baseline associated with asthma events, and evaluate algorithms capable of identifying triggers and predicting asthma control changes from baseline data. Patient experience and compliance with the devices were also explored.

Design: This was a multicenter, observational, 24-week, proof-of-concept study conducted in the United States.

Methods: Patients (⩾12 years) with severe, uncontrolled asthma engaged with a spirometer, vital sign monitor, sleep monitor, connected inhaler devices, and two mobile applications with embedded patient-reported outcome (PRO) questionnaires. Prospective data were linked to data from electronic health records and transmitted to a secure platform to develop predictive algorithms. The primary endpoint was an asthma event: symptom worsening logged by patients (PRO); peak expiratory flow (PEF) < 65% or forced expiratory volume in 1 s < 80%; increased short-acting β₂-agonist (SABA) use (>8 puffs/24 h or >4 puffs/day/48 h). For each endpoint, predictive models were constructed at population, subgroup, and individual levels.

Results: Overall, 108 patients were selected: 66 (61.1%) completed and 42 (38.9%) were excluded for failure to respond/missing data. Predictive accuracy depended on endpoint selection. Population-level models achieved low accuracy in predicting endpoints such as PEF < 65%. Subgroups related to specific allergies, asthma triggers, asthma types, and exacerbation treatments demonstrated high accuracy, with the most accurate, predictive endpoint being >4 SABA puffs/day/48 h. Individual models, constructed for patients with high endpoint overlap, exhibited significant predictive accuracy, especially for PEF < 65% and >4 SABA puffs/day/48 h.

Conclusion: This multidimensional dataset enabled population-, subgroup-, and individual-level analyses, providing proof-of-concept evidence for development of predictive models of fluctuating asthma control.

Mucormycosis is an invasive fungal infection that can result in severe lung infections, with pulmonary mucormycosis (PM) being one of the most prevalent manifestations. Prompt diagnosis is crucial for patient survival, as PM often exhibits rapid clinical progression and carries a high fatality rate. Broncho-alveolar lavage fluid or endobronchial biopsy (EBB) has been commonly employed for diagnosing PM, although there is limited mention of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the literature. In this report, we present a case of PM in a patient with diabetes. While EBB did not yield evidence of Rhizopus infection, a definitive diagnosis was obtained through EBUS-TBNA. The patient underwent combination therapy, including oral medication, nebulization, and EBUS-guided intrafocal amphotericin B injection, which resulted in significant improvement following the failure of initial therapy with amphotericin B injection cholesterol sulfate complex. Our case highlights the potential of EBUS-TBNA not only for mediastinal lymphadenopathy but also for obtaining extraluminal lesion specimens. Furthermore, for patients with an inadequate response to mono-therapy and no access to surgical therapy, the addition of EBUS-guided intralesional amphotericin B injection to systemic intravenous therapy may yield unexpected effects.

Background: Coronavirus disease (COVID)-19 can lead to chronic lung damage and respiratory issues, potentially increasing surgical difficulty and risk for patients with non-small-cell lung cancer (NSCLC). However, the impacts of a COVID-19 history on early outcomes in NSCLC patients remain controversial.

Objectives: To evaluate the effect of COVID-19 history on early outcomes in NSCLC patients and identify high-risk groups undergoing radical resection based on the largest Chinese multi-center real-world data to date.

Design: Multi-center retrospective cohort study.

Methods: NSCLC patients with (POCVD group) or without (NCVD group) a history of COVID-19 who underwent radical surgery at six institutions from January 2022 to January 2024 were retrospectively reviewed from a prospectively maintained database. Propensity-score matching (PSM) was utilized to minimize patient selection bias.

Results: Out of 7932 cases included, PSM resulted in 3021 cases per group. The two groups were comparable regarding the proportion of male patients (52.0% vs 51.6%) and those aged ⩾70 years (13.3% vs 13.8%). Although the two groups had comparable incidences of complications with Clavien-Dindo grades ⩾II (13.0% vs 14.4%, p = 0.117), the POCVD group had longer surgical durations (120.87 ± 40.23 min vs 110.74 ± 38.76 min, mean difference (95% confidence interval (CI) = 10.13 (8.138-12.122)) and higher rates of respiratory complications than the NCVD group. Subgroup logistic regression analysis indicated that patients aged ⩾70 years (odds ratio (OR) (95% CI) = 1.322 (1.022-1.876)) and those with a smoking history (OR (95% CI) = 1.235 (1.008-1.543)) had an increased risk of developing complications with Clavien-Dindo grades ⩾II. Further analysis confirmed that these high-risk patients experienced extended surgical durations, longer chest tube drainage, and prolonged postoperative hospital stay, along with increased postoperative respiratory complications following COVID-19.

Conclusion: Generally, radical resection is safe for NSCLC patients with a COVID-19 history. However, these patients experienced prolonged surgical durations and a higher incidence of postoperative respiratory complications compared to those without a COVID-19 history. In addition, individuals aged ⩾70 years or with a smoking history faced elevated surgical risks following COVID-19.

Background: Gut-blood and blood-brain barrier permeabilty (gut-brain axis) has been attracting increased attention in the etiology of neurodevelopmental disorders. In this study, we aimed to investigate serum levels of zonulin (a biomarker of intestinal permeability), claudin-5 (a biomarker of blood-brain barrier permeability), and interferon-gamma and interleukin-17A in children with specific learning disorder.

Methods: Forty-three children with DSM-5 diagnosis of specific learning disorder and 43 healthy children were included in this study. Serum levels of zonulin, claudin-5, interferon-gamma, and interleukin-17A were measured using commercial enzyme-linked immunosorbent assay kits.

Results: Serum zonulin and claudin-5 levels of the study group were significantly higher than the control group according to the multivariate analysis of covariance test while controlling for age, gender, and body mass index. However, serum interferon-gamma and interleukin-17A levels were not significantly different between the two groups. There was no correlation either between zonulin and interferon-gamma and interleukin-17A or claudin-5 and interferon-gamma and interleukin-17A.

Conclusion: Gut-blood and blood-brain barrier permeability may be disrupted in subjects with special learning disorder. Further research is needed to determine whether zonulin and claudin-5 may be biomarkers, and some dietary interventions or specific agents such as zonulin or claudin-5 inhibitors could be used in the management of neurodevelopmental disorders including special learning disorder.