Therapeutic Advances in Respiratory Disease最新文献

Background: The small airway disease has been recognized as a central feature of chronic obstructive pulmonary disease (COPD). Triple fixed combination beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) is provided as a pressurized single-dose inhaler based on an extra-fine formulation, which has been approved for patients with COPD experiencing frequent disease exacerbations.

Methods: The aim of our real-life single-center observational study was to investigate, in 22 patients with COPD, the effects of BDP/FF/G on lung function, respiratory symptoms, health status, and exacerbation rate. Several clinical and lung functional parameters were evaluated at baseline and after 12 months of treatment with combined inhaled triple therapy.

Results: With respect to baseline, after 12 months of treatment with BDP/FF/G, significant changes were recorded with regard to forced expiratory flow at 75% of forced vital capacity (FVC) (p < 0.01), forced expiratory flow at 50% of FVC (p < 0.01), forced expiratory flow at 25% of FVC (p < 0.05), and forced mid-expiratory flow between 25% and 75% of FVC (p < 0.01). Moreover, we observed reductions of total resistance (p < 0.01), effective resistance (p < 0.01), and effective specific resistance (p < 0.01). In the same period, residual volume diminished (p < 0.01) and forced expiratory volume in 1 s increased (p < 0.01). Moreover, in a subgroup of 16 patients, an enhancement of diffusion lung capacity (p < 0.01) was also detected. These functional results were paralleled by concomitant clinical effects, as evidenced by the improvements of modified British Medical Research Council (mMRC) dyspnea scale (p < 0.001), COPD Assessment Test (CAT) score (p < 0.0001), and COPD exacerbations (p < 0.0001).

Conclusion: In conclusion, the valuable findings of our observational study consist in the corroboration in a real-life context of the therapeutic effects evidenced by randomized controlled trials with regard to the use of the triple inhaled BDP/FF/G therapy in patients with COPD.

Background: N-acetylcysteine (NAC) may reduce acute exacerbations of chronic obstructive pulmonary disease through an antioxidant effect. Due to the heterogeneity in studies, the currently available data do not confirm the efficacy of oral NAC therapy in chronic obstructive pulmonary disease patients. We hypothesize that chronic obstructive pulmonary disease patients receiving regular oral NAC therapy do not achieve improved clinical outcomes.

Objectives: The purpose of this meta-analysis was to determine the efficacy of long-term oral NAC therapy in chronic obstructive pulmonary disease patients.

Data sources and methods: The literature search was performed using the PubMed, Web of Science, and Cochrane Library databases to identify all included clinical studies. Studies were eligible for inclusion only if they directly compared the outcomes of NAC versus placebo in adults with chronic obstructive pulmonary disease between 1 January 2000 and 30 May 2022. All studies were included if they reported one or more of the following outcomes: number of patients with no acute exacerbations, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), St George's Respiratory Questionnaire score, glutathione level, and adverse events.

Results: Nine randomized controlled trials were included in the meta-analysis. There were 1061 patients in the NAC group and 1076 patients in the placebo group. The current meta-analysis provides evidence that the number of patients with no acute exacerbations (965 patients receiving NAC therapy, 979 control group patients), change in FEV1 (433 patients receiving NAC therapy, 447 control group patients), change in FVC (177 patients receiving NAC therapy, 180 control group patients), change in St George's Respiratory Questionnaire score (128 patients receiving NAC therapy, 131 control group patients), change in glutathione levels (38 patients receiving NAC therapy, 40 control group patients), and adverse events (832 patients receiving NAC therapy, 846 control group patients) were not significantly different between the two groups.

Conclusion: NAC did not reduce the risk of acute exacerbation or ameliorate the decline in lung volume in chronic obstructive pulmonary disease patients.

Background: There is little information on the optimal storage conditions for recovery of nontuberculous Mycobacterium spp. (NTM) from refrigerated sputum.

Objectives: We investigated the storage duration that could increase the culture-positive rate of NTM isolates.

Design: In this prospective study, we collected NTM isolates and clinical data from patients with repeated culture-positive NTM pulmonary disease (NTM-PD).

Methods: From June 2020 to July 2021, the participants were instructed to randomly collect six sputum samples and immediately store them in a refrigerator at 4°C until the date of their clinic visit. At the outpatient visits, expectorated spot sputum samples were collected.

Results: A total of 226 sputum samples were collected from 35 patients. The median duration of refrigeration was 6 days (maximum duration: 36 days). The overall culture-positive rate was 81.6%. While there was a trend for a higher culture positivity rate when stored for ⩽3 weeks, this was not significant compared with those stored for >3 weeks (p = 0.610). According to sputum microscopy, smear-positive sputum was 100% isolated, but smear-negative samples had a culture-positive rate of 77.5%. Similarly, there was no significant association between sputum storage duration and culture positivity (p = 0.511). In addition, the recovery rate of the refrigerated sputum was comparable with the collected spot expectorated sputum (82.6% versus 80.6%, p = 0.795), which is suggestive of the long-term viability of NTM in refrigerated sputum.

Conclusion: Our data demonstrated the long-term viability of refrigerated NTM, and the culture positivity rate of these samples was comparable with the spot expectorated sputum. These results suggest that implementing sputum refrigeration would enhance convenience in diagnosing and following patients with NTM-PD.

Plain language summary: Easy way to diagnose NTM lung diseasesUnder usual circumstances, most patients with suspected NTM submit spontaneously expectorated sputum rather than induced sputum for the purpose of testing the causative organism. By collecting and storing sputum specimens for a longer period than before, it is expected that more sufficient and adequate collection of sputum specimens will be possible.

The article traces the concept of asthma control within GINA guidelines over the past 25 years. In the first 15 years after 1995, the main objective of asthma management was to obtain the control of all clinical and functional characteristics of asthma. A landmark study (GOAL) showed for the first time that a good control of asthma is a reasonable outcome that can be achieved in a large proportion of asthmatics with a regular appropriate treatment. In the following years, more emphasis was placed on the role of exacerbations as critical manifestations of poor asthma control, whose frequency is associated with excessive FEV1 decline and increased risk of death. Accordingly, the 2014 GINA report makes a clear distinction between the control of the day-by-day symptoms and the reduction in the risk of severe exacerbations, stating that both conditions should be obtained. The 2019 update included a significant change in the management of mild asthma, prioritizing the prevention of exacerbations to that of mild symptoms. This view was repeated in the 2021 update, where the prevention of exacerbations, together with an acceptable symptom control with a minimal use of rescue medication, appeared to be the real main goal of asthma management. While a discrepancy between current symptoms and exacerbations may be present in mild asthma, a significant relationship between these two features is observed in moderate-severe asthma: a persistent poor symptom control is a major risk factor for exacerbations, whereas achieving symptom control through regular treatment is associated with a reduction in exacerbation rate. Thus, the opinion that frequent symptoms are not important in the absence of acute exacerbations should be discouraged, whereas education of patients to a good symptom perception and to improve adherence to regular treatment should be implemented. Furthermore, the persistence of risk factors, such as increased airway inflammation, even in a patient with minor daily symptoms, should be considered for optimizing treatment.

Background: The long-term efficacy of the Dumon stent in the treatment of benign airway stenosis is unclear.

Objective: The objective of this study was to evaluate the long-term efficacy and safety of the Dumon stent in patients with benign airway stenosis.

Methods: We retrospectively reviewed patients with benign airway stenosis who were treated with a Dumon stent at the First Affiliated Hospital of Guangzhou Medical University between March 2014 and October 2021. We included patients with successful removal of silicone stents after implantation. The clinical data and information on bronchoscopic interventional procedures and related complications were collected and analyzed.

Results: Ninety-nine patients with benign airway stenosis were included. The stent was placed mainly in the trachea (44.4%) and left main bronchus (43.4%). The main type of stenosis was post-tuberculosis bronchial stenosis (57.6%). The overall cure rate was 60.6%. Stent-related complications included retention of secretions (70.7%), granuloma formation (67.7%), stent angulation (21.2%), and stent migration (12.1%). The stent was less effective for left main bronchus stenosis (p = 0.012). Multivariate logistic regression analysis identified that stent placement for more than 13 months, a stent-intervention number of ⩽ 1 predicted a favorable outcome.

Conclusion: The efficacy and safety of the Dumon stent for benign airway stenosis need improvement. The stent is less effective for left main bronchus stenosis; regular follow-up is required in such cases. Stent placement for > 13 months and no more than once stent intervention within a 6-month period were associated with a favorable outcome.

Background: The management of refractory chronic cough (RCC) is a great challenge. Neuromodulators have long been used for RCC with imperfect efficacy.

Objectives: We summarized the outcomes of the current treatments used at our specialist cough clinic, which provides a guideline-led service and real-world experience for the future management of RCC.

Design: This is a single-centre retrospective observational cohort study.

Methods: Consecutive RCC patients (the first clinic visit between January 2016 and May 2021) were included into this observational cohort study. Medical records in the Chronic Cough Clinical Research Database were fully reviewed using uniform criteria. The included subjects were followed-up for at least 6 months after the final clinic visit via instant messages with the link to self-scaled cough-associated questionnaires.

Results: Overall, 369 RCC patients were analysed with a median age of 46.6 years and a cough duration of 24.0 months. A total of 10 different treatments were offered. However, 96.2% of patients had been prescribed at least one neuromodulator. One-third of patients had alternative treatments prescribed given the poor response to the initial therapy and 71.3% favourably responded to at least one of the treatments. Gabapentin, deanxit, and baclofen had comparable therapeutic efficacy (56.0%, 56.0%, and 62.5% respectively; p = 0.88) and overall incidences of adverse effects (28.3%, 22.0%, and 32.3% respectively; p = 0.76). However, 19.1 (7.7-41.8) months after the last clinic visit, 65.0% reported improvement (24.9%) or control of their cough (40.1%); 3.8% reported a spontaneous remission and 31.2% still had a severe cough. Both HARQ (n = 97; p < 0.001) and LCQ (n = 58; p < 0.001) demonstrated marked improvement.

Conclusion: Trying different neuromodulators is a pragmatic strategy for RCC, which helped around two-thirds of patients. Relapse is common on withdrawal or reduction of dosage. Novel medication for RCC is an urgent clinical need.

Plain language summary: This is the first report that fully represented a guideline-led treatment protocol for refractory chronic cough (RCC) based on a large series of patients, which evaluated the short- and long-term effects of the currently available treatments for RCC. We found that the therapeutic trial of different neuromodulators is a pragmatic strategy, which helped around two-thirds of patients. Gabapentin, deanxit (flupentixol/melitracen), and baclofen had similar therapeutic outcomes. This study may offer real-world experience for the future management of RCC.

Background: Evidence suggests differences in ventilation efficiency and respiratory mechanics between early COVID-19 pneumonia and classical acute respiratory distress syndrome (ARDS), as measured by established ventilatory indexes, such as the ventilatory ratio (VR; a surrogate of the pulmonary dead-space fraction) or mechanical power (MP; affected, e.g., by changes in lung-thorax compliance).

Objectives: The aim of this study was to evaluate VR and MP in the late stages of the disease when patients are ready to be liberated from the ventilator after recovering from COVID-19 pneumonia compared to respiratory failures of other etiologies.

Design: A retrospective observational cohort study of 249 prolonged mechanically ventilated, tracheotomized patients with and without COVID-19-related respiratory failure.

Methods: We analyzed each group's VR and MP distributions and trajectories [repeated-measures analysis of variance (ANOVA)] during weaning. Secondary outcomes included weaning failure rates between groups and the ability of VR and MP to predict weaning outcomes (using logistic regression models).

Results: The analysis compared 53 COVID-19 cases with a heterogeneous group of 196 non-COVID-19 subjects. VR and MP decreased across both groups during weaning. COVID-19 patients demonstrated higher values for both indexes throughout weaning: median VR 1.54 versus 1.27 (p < 0.01) and MP 26.0 versus 21.3 Joule/min (p < 0.01) at the start of weaning, and median VR 1.38 versus 1.24 (p < 0.01) and MP 24.2 versus 20.1 Joule/min (p < 0.01) at weaning completion. According to the multivariable analysis, VR was not independently associated with weaning outcomes, and the ability of MP to predict weaning failure or success varied with lung-thorax compliance, with COVID-19 patients demonstrating consistently higher dynamic compliance along with significantly fewer weaning failures (9% versus 30%, p < 0.01).

Conclusion: COVID-19 patients differed considerably in ventilation efficiency and respiratory mechanics among prolonged ventilated individuals, demonstrating significantly higher VRs and MP. The differences in MP were linked with higher lung-thorax compliance in COVID-19 patients, possibly contributing to the lower rate of weaning failures observed.

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) that results from an immune-mediated reaction involving various antigens in susceptible individuals. However, the clinical characteristics and outcomes of HP in South Korea are not well understood.

Objectives: This study was conducted to identify the clinical characteristics and outcomes of HP in South Korea.

Design: This is a retrospective observational study investigating patients with pathologically confirmed HP at our center, along with a comprehensive review of published HP cases in the Republic of Korea.

Methods: This retrospective study analyzed 43 patients with pathologically proven HP at a single tertiary hospital in Korea between 1996 and 2020. In addition, case reports of HP published in Korea were collected. The clinical characteristics, etiologies, treatment, and outcomes of patients from our center, as well as case reports, were reviewed. Patients from our hospital were divided into fibrotic and nonfibrotic subtypes according to the ATS/JRS/ALAT guidelines.

Results: Among 43 patients with biopsy-proven HP, 12 (27.9%) and 31 (72.1%) patients were classified into the fibrotic and nonfibrotic subtypes, respectively. The fibrotic HP group was older (64.6 ± 8.5 versus 55.2 ± 8.3, p = 0.002) with less frequent complaints of fever (0% versus 45.2%, p = 0.013) compared to the nonfibrotic HP group. The most common inciting antigen was household mold (21, 48.8%), followed by inorganic substances (6, 14.0%). Inciting antigens were not identified in eight (18.6%) patients. Treatment of corticosteroids was initiated in 34 (79.1%) patients. An analysis of 46 patients from Korea by literature review demonstrated that reported cases were relatively younger and drugs were the most common etiology compared to our cohort.

Conclusion: The analysis of reported cases, as well as our cohort, showed that exposure history and clinical manifestations are heterogeneous for patients with HP in South Korea.

Objective: Pulmonary rehabilitation (PR) has been considered to be an effective treatment method for various respiratory diseases. However, the effects of exercise-based PR on patients with severe/very severe chronic obstructive pulmonary disease (COPD) are unclear. This review aimed to investigate the effects of exercise-based PR on patients with severe/very severe COPD.

Methods: PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were searched from inception to December 23, 2022, without language restrictions. Randomized controlled trials (RCTs) investigating the effects of exercise-based PR on patients with severe/very severe COPD were included. Study selection, data extraction, and risk of bias assessment were conducted independently. RevMan software (version 5.3) was used for meta-analysis. The quality of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation system.

Results: Six studies (263 patients) were identified. Compared with the control group, the 6-min walking distance [MD = 52.91, 95% CI (3.80, 102.03)], the St. George's Respiratory Questionnaire total scores [MD = -7.70, 95% CI (-14.32, -1.08)] and the Borg scale scores [MD = -0.68, 95% CI (-1.28, -0.08)] in the experimental group improved, respectively. The St. George's Respiratory Questionnaire and Borg scale scores were rated as 'moderate quality' and 'low quality', respectively, and the 6-min walking distance was rated as 'very low quality'.

Conclusions: Exercise-based PR may improve the exercise capacity, quality of life and dyspnea of patients with severe/very severe COPD, which can be regarded as an adjuvant treatment. High quality and large sample RCTs are needed.

Registration: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (No. CRD42022294085).