Therapeutic Advances in Respiratory Disease最新文献

Background: A six-minute walk test (6MWT) is a reproducible, easily performed test, and is widely used to determine functional exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). However, there is currently a paucity of data on the clinical significance of baseline and serial 6-minute walk tests in patients with IPF, especially in Asian patients.

Objectives: We aimed to investigate the clinical significance of serial 6MWT in patients with IPF, especially in Asian patients.

Design: This is a single-center retrospective cohort study.

Methods: Clinical data of patients diagnosed with IPF at a tertiary center in Korea were retrospectively analyzed. IPF diagnosis was defined according to the clinical guidelines of the American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society/Latin American Thoracic Association.

Results: There were 216 patients diagnosed with IPF from December 2012 to January 2022, of whom 198 had a baseline of 6MWT data. The mean age of the cohort was 66.9 ± 8.6, and 89% were male. The non-survivors showed significantly lower six-minute walk distance (6MWD), minimum saturation of peripheral oxygen (SpO₂) during 6MWT, forced vital capacity, and diffusing capacity of the lung for carbon monoxide than survivors at baseline. A multivariate Cox analysis demonstrated that lower minimum SpO₂ was independently associated with increased mortality rates (Hazard ratio (HR): 1.081, 95% confidence interval (CI): 1.024-1.142, p = 0.005). Higher mortality rates were also associated with echocardiographic-determined pulmonary hypertension (HR: 2.466, 95% CI: 1.149-5.296, p = 0.021) at diagnosis. Among 144 patients with 6MWT results at 12 months, patients with a decline of 50 m or more in the 6MWD showed poorer overall survival than others (median survival: 45.0 months vs 58.0 months, p < 0.001).

Conclusions: Baseline lower minimum SpO₂ during 6MWT was an independent prognostic factor in patients with IPF, and a decline in 6MWD in serial follow-up was also associated with a poorer prognosis. These findings suggest that both baseline 6MWT and follow-up data are important in the prognostication of patients with IPF.

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: 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: 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.

In recent years, a new test method namely the cough suppression test has been proposed to measure cough suppression in patients with chronic cough. The cough suppression test is a modified test based on capsaicin tussive challenge. There are similarities and differences between it and the more established cough challenge test in detection method, purpose and clinical significance. In this article, we will introduce and compare the concepts, application and methodology of the cough suppression test and the cough challenge test, summarize this research progress and problems of the two methods, and predict the possible role of both in the further study of chronic cough.

Background: Prone positioning (PP) is an established and commonly used lung recruitment method for intubated patients with severe acute respiratory distress syndrome, with potential benefits in clinical outcome. The role of PP outside the intensive care unit (ICU) setting is debated.

Objectives: We aimed at assessing the role of PP in death and ICU admission in non-intubated patients with acute respiratory failure related to COronaVIrus Disease-19 (COVID-19) pneumonia.

Design: This is a retrospective analysis of a collaborative multicenter database obtained by merging local non-interventional cohorts.

Methods: Consecutive adult patients with COVID-19-related respiratory failure were included in a collaborative cohort and classified based on the severity of respiratory failure according to the partial arterial oxygen pressure to fraction of inspired oxygen ratio (PaO₂/FiO₂) and on clinical severity by the quick Sequential Organ Failure Assessment (qSOFA) score. The primary study outcome was the composite of in-hospital death or ICU admission within 30 days from hospitalization.

Results: PP was used in 114 of 536 study patients (21.8%), more commonly in patients with lower PaO₂/FiO₂ or receiving non-invasive ventilation and less commonly in patients with known comorbidities. A primary study outcome event occurred in 163 patients (30.4%) and in-hospital death in 129 (24.1%). PP was not associated with death or ICU admission (HR 1.17, 95% CI 0.78-1.74) and not with death (HR 1.01, 95% CI 0.61-1.67) at multivariable analysis; PP was an independent predictor of ICU admission (HR 2.64, 95% CI 1.53-4.40). The lack of association between PP and death or ICU admission was confirmed at propensity score-matching analysis.

Conclusion: PP is used in a non-negligible proportion of non-intubated patients with COVID-19-related severe respiratory failure and is not associated with death but with ICU admission. The role of PP in this setting merits further evaluation in randomized studies.

Background: Idiopathic pulmonary fibrosis (IPF) is a known risk factor for venous thromboembolism (VTE). However, it is currently unknown which factors are associated with an increase of VTE in patients with IPF.

Objectives: We estimated the incidence of VTE in patients with IPF and identified clinical characteristics related to VTE in patients with IPF.

Design and methods: De-identified nationwide health claim data from 2011 to 2019 was collected from the Korean Health Insurance Review and Assessment database. Patients with IPF were selected if they had made at least one claim per year under the J84.1 [International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10)] and V236 codes of rare intractable diseases. We defined the presence of VTE as at least one claim of pulmonary embolism and deep vein thrombosis ICD-10 codes.

Results: The incidence rate per 1000 person-years of VTE was 7.08 (6.44-7.77). Peak incidence rates were noted in the 50-59 years old male and 70-79 years old female groups. Ischemic heart disease, ischemic stroke, and malignancy were associated with VTE in patients with IPF, with an adjusted hazard ratio (aHR) of 1.25 (1.01-1.55), 1.36 (1.04-1.79), and 1.53 (1.17-2.01). The risk for VTE was increased in patients diagnosed with malignancy after IPF diagnosis (aHR = 3.18, 2.47-4.11), especially lung cancer [hazard ratio (HR) = 3.78, 2.90-4.96]. Accompanied VTE was related to more utilization of medical resources.

Conclusion: Ischemic heart disease, ischemic stroke, and malignancy, especially lung cancer, were related to higher HR for VTE in IPF.