ERJ Open Research最新文献

Background: In response to exercise-based pulmonary rehabilitation (PR), the type of muscle fibre remodelling differs between COPD patients with peripheral muscle wasting (atrophic patients with COPD) and those without wasting (nonatrophic patients with COPD). Extracellular matrix (ECM) proteins are major constituents of the cell micro-environment steering cell behaviour and regeneration. We investigated whether the composition of ECM in atrophic compared to nonatrophic patients with COPD differs in response to PR.

Methods: Vastus lateralis muscle biopsies from 29 male COPD patients (mean±sem forced expiratory volume in 1 s: 43±6% predicted) classified according to their fat-free mass index as atrophic (<17 kg·m^-2, n=10) or nonatrophic (≥17 kg·m^-2, n=19) were analysed before and after a 10-week PR programme for myofibre distribution and size, whereas a selection of ECM molecules was quantified using ELISA and real-time PCR.

Results: In nonatrophic patients with COPD PR was associated with increased myofibre type I distribution (by 6.6±2.3%) and cross-sectional area (CSA) (by 16.4±4.8%), whereas in atrophic patients with COPD, PR induced increased myofibre type IIa distribution (by 9.6±2.8%) and CSA (by 12.1±3.2%). PR induced diverse intramuscular ECM adaptations in atrophic compared to nonatrophic patients with COPD. Accordingly, following PR there was a significant increase in protein levels of ECM biomarkers (collagen type I by 90 pg·mL^-1; collagen type IV by 120 pg·mL^-1; decorin by 70 pg·mL^-1) only in nonatrophic patients with COPD. Conversely, post-PR, osteopontin, a protein known for its dystrophic effects, and tenacin C, a necroptosis compensatory factor facilitating muscle regeneration, were upregulated at protein levels (by 280 pg·mL^-1and 40 pg·mL^-1, respectively) in atrophic patients with COPD, whereas fibronectin protein levels were decreased.

Conclusions: These findings suggest that the differential PR-induced myofibre adaptations in atrophic compared to nonatrophic patients with COPD could be associated with inadequate remodelling of the intramuscular ECM environment.

This editorial discusses the article by Coldet al. demonstrating improvements in bronchoscopy on a model when aided by artificial intelligence (AI) software. It explores hypothetical benefits and concerns stemming from AI-enhanced bronchoscopy. https://bit.ly/3BAExJs.

Background: Small airway dysfunction (SAD) and impaired diffusion capacity of the lungs for carbon monoxide (D _LCO) are positively associated with a worse prognosis. Individuals with both dysfunctions have been identified in clinical practice and it is unknown whether they have worse health status or need management. We conducted this study to explore the association between SAD and impaired D _LCO, and the difference between the groups with two dysfunctions, with either one dysfunction and with no dysfunction.

Methods: This study involved subjects partly from those who had returned for the third-year follow-up (up to December 2022) of the Early Chronic Obstructive Pulmonary Disease study and those who newly participated. We assessed diffusion capacity, questionnaire, exacerbations, spirometry, impulse oscillometry (IOS) and computed tomography (CT). Impaired D _LCO was defined as D _LCO <80% predicted. Spirometry-defined SAD was defined using the percent predicted values of maximal mid-expiratory flow, and forced expiratory flow at 50% and 75% of forced vital capacity, at least two of these three values being <65% predicted after the use of a bronchodilator. IOS-defined SAD was defined when the difference in resistance at 5 and 20 Hz was >0.07 kPa·L^-1·s. CT-defined SAD was defined when the percentage of expiratory low-attenuation areas <-856 HU comprised ≥15% of the total lung volume. Covariate analyses and logistic regression were performed to assess the association between impaired D _LCO and SAD.

Results: This study involved 581 subjects. The occurrence of both spirometry- and CT-defined SAD was significantly higher in subjects with impaired D _LCO than normal D _LCO. Subjects with two dysfunctions were associated with worse preceding year's exacerbations than controls.

Conclusions: Impaired diffusion capacity is positively associated with SAD. Subjects with impaired diffusion capacity and SAD may have a worse health status and need additional management.

Background: Chronic cough (CC) is underevaluated and underreported. The introduction of a tool that is easy to complete, score and interpret and with the psychometric properties requested for use in individual patients could improve clinical practice.

Objective: This cross-sectional study aimed to validate the Chronic Cough Patient Perspective (CCPP) for assessing CC in daily practice.

Methods: A provisional CCPP was created by iteratively reducing the Chronic Cough Impact Questionnaire (CCIQ). Its psychometric properties were tested in CC patients at baseline (visit 1) and after 1 month (visit 2).

Results: The reduction process yielded an 8-item provisional version, subsequently validated in 150 patients (36.33% males, mean age 50±16.9 years). Exploratory factor analysis revealed a one-dimensional structure, with one item being deleted as it did not align with the extracted dimension. The 7-item version of the CCPP showed a strong correlation with the CCIQ (r=0.902 at visit 1, r=0.932 at visit 2) and internal consistency (Cronbach's alpha values: 0.85 at visit 1, 0.93 at visit 2); discriminant and convergent validity were satisfactory. The reliability, assessed in 21 patients with no change in CC (Global Rating Scale=0), was high (concordance correlation coefficient=0.815; interclass coefficient=0.823). A score ≤5 indicates optimal health-related quality of life (HRQoL) attainment, with a minimum important difference of 3. The mean CCPP score was 20.5±6.24 at enrolment, and only 37.33% of the participants achieved an optimal HRQoL at visit 2.

Conclusion: The CCPP exhibited good psychometric properties suitable for clinical use, providing a valid, reliable and standardised assessment of CC's impact on HRQoL.

Background: Data regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with a very low 6-min walk test (6MWT) are limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutic benefits and increased complication risk.

Study designs and methods: This study utilised data from the Lungenemphysemregister e.V., a large German national multi-centre prospective open-label clinical trial, and aimed to assess the outcomes of ELVR in patients with a baseline 6MWT ≤140 m and dyspnoea primarily attributed to hyperinflation.

Results: 54 patients with a baseline 6MWT ≤140 m and 365 patients with a baseline 6MWT between 140 and 450 m were included in the study. Baseline characteristics were representative for patients with advanced lung emphysema. Patients with a 6MWT ≤140 m at baseline had a lower forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide and higher symptom burden. In the 3-month follow-up, patients of both groups showed statistically significant improvements in lung function parameters, exercise capacity and quality of life parameters compared to baseline. Patients with a 6MWT ≤140 m at baseline showed significantly more 6MWT improvement compared to patients with baseline 6MWT between 140 and 450 m. Moreover, complication rates were similar in both groups.

Interpretation: In summary, the data indicate that ELVR may be an effective and safe treatment for emphysema patients with a very low 6MWT of ≤140 m if very limited exercise capacity is predominately caused by lung emphysema. Therefore future studies should include emphysema patients with a very low 6MWT.

Introduction: Achieving an early diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in pulmonary embolism (PE) survivors results in better quality of life and survival. Importantly, dedicated follow-up strategies to achieve an earlier CTEPH diagnosis involve costs that were not explicitly incorporated in the models assessing their cost-effectiveness. We performed an economic evaluation of 11 distinct PE follow-up algorithms to determine which should be preferred.

Materials and methods: 11 different PE follow-up algorithms and one hypothetical scenario without a dedicated CTEPH follow-up algorithm were included in a Markov model. Diagnostic accuracy of consecutive tests was estimated from patient-level data of the InShape II study (n=424). The lifelong costs per CTEPH patient were compared and related to quality-adjusted life-years (QALYs) for each scenario.

Results: Compared to not performing dedicated follow-up, the integrated follow-up algorithms are associated with an estimated increase of 0.89-1.2 QALYs against an incremental cost-effectiveness ratio (ICER) of EUR 25 700-46 300 per QALY per CTEPH patient. When comparing different algorithms with each other, the maximum differences were 0.27 QALYs and EUR 27 600. The most cost-effective algorithm was the InShape IV algorithm, with an ICER of EUR 26 700 per QALY compared to the next best algorithm.

Conclusion: Subjecting all PE survivors to any of the currently established dedicated follow-up algorithms to detect CTEPH is cost-effective and preferred above not performing a dedicated follow-up, evaluated against the Dutch acceptability threshold of EUR 50 000 per QALY. The model can be used to identify the locally preferred algorithm from an economical point-of-view within local logistical possibilities.

Introduction: Exposure to environmental factors (i.e. air pollution and second-hand tobacco smoke) have been associated with impaired lung function. However, the impact of environmental factors on lung health is usually evaluated separately and not with an exposomic framework. In this regard, breath analysis could be a noninvasive tool for biomonitoring of global human environmental exposure.

Methods: Data come from 337 mother-child pairs from the Nutrition in Early Childhood Asthma (NELA) birth cohort. Levels of BTEX (benzene, toluene, ethylbenzene and xylenes) in exhaled breath from mothers and children at 3 months after birth were estimated using gas chromatography-mass spectrometry. Short-term residential exposures (breath sampling day and 15 days before breath sampling) to nitrogen dioxide, particulate matter (PM_2.5) and ozone were determined by chemical dispersion/transport modelling. Forced vital capacity, forced expiratory volume in 0.5 s (FEV_0.5) and forced expiratory flow at 75% of FVC and at 25%-75% of FVC were measured in infants according to the raised-volume rapid thoracoabdominal compression technique.

Results: The results showed significant associations between short-term exposure to external agents and levels of benzene and toluene in exhaled breath. It was observed that exhaled levels of benzene and toluene were influenced by smoking status and outdoor air pollution in mothers, and by air pollution in infants (3 months of age). No significant relationship was observed between exposure to maternal tobacco smoking and/or short-term air pollution and lung function in healthy infants. However, there was a significant relationship between FEV_0.5 and exhaled toluene in children.

Discussion: These findings indicated a significant relationship between environmental exposures and exhaled levels of benzene and toluene, suggesting that breath analysis could be a helpful exposure biomonitoring tool.

Background: Remote patient monitoring (RPM) has been evaluated in COPD, but with varying results. We aimed to evaluate whether a tablet system that monitors disease-related parameters in patients with COPD could influence physical and mental health-related quality of life, compared with usual care (UC).

Methods: 70 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D COPD (61% women, aged 71±8 years, forced expiratory volume in 1 s % predicted 41±13%, COPD Assessment Test (CAT) 19±7 points) were recruited at the COPD centre in Gothenburg, Sweden, and randomised to a tablet-based RPM system or UC for a 26-week period, after which they crossed over to the alternative management for another 26 weeks. The Short Form-12 (SF-12) (primary outcome), CAT, modified Medical Research Council (mMRC) Dyspnoea Scale, EuroQol-5 Dimensions (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) were evaluated at four visits. Exacerbations were continuously reported, as was adherence to RPM.

Results: 59 patients completed the study: 28 patients randomised to start with UC and 31 randomised to start with RPM. The changes in the SF-12 Physical Component Summary (PCS) (UC: -1.17±6.90 versus RPM: -1.06±8.15) and Mental Component Summary (MCS) (UC: 0.63±11.14 versus RPM: -0.63±8.15), as well as in CAT, the mMRC scale, the EQ-5D, HADS anxiety, HADS depression and number of exacerbations, were similar in both intervention periods. Neither the 26-week UC period nor the intervention significantly affected the measured outcomes. There was a 95% adherence rate during RPM.

Conclusions: A 26-week tablet-based RPM system that monitors CAT, oxygen saturation, blood pressure, pulse, weight and physical activity, connected to a case manager, is feasible and safe, but did not influence health-related quality of life in patients with COPD GOLD D.

Since being published in 2021 in ERJ Open Research, a self-help resource has been made widely available to adults with PH in the UK via PHA UK. This is an update on the continued impact of the intervention hearing from services users and PHA UK. https://bit.ly/3YLHIHm.

Introduction: Refractory chronic cough (RCC), persisting despite addressing contributory diagnoses, is likely underpinned by neurally mediated cough hypersensitivity. RFC1 disorders are genetic neurodegenerative conditions caused by biallelic RFC1 repeat expansion sequences, commonly presenting with cough, followed by neurological features including cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). The prevalence and identifying clinical characteristics of RFC1 repeat-expansion disorders in patients with RCC are unknown.

Methods: Consecutive patients with RCC underwent RFC1 genotyping, cough severity visual analogue scale (VAS) and cough-specific health status assessment (Leicester Cough Questionnaire (LCQ)). Participants with biallelic RFC1 repeat expansions (RFC1⁺⁺) also underwent nerve conduction studies, brain imaging (MRI) and cough reflex sensitivity testing.

Results: 51 participants with RCC were recruited; 36 (71%) female, median (IQR) age 65 (56-70) years, duration of cough 12.8 (6.9-20.0) years. Four (8%) were RFC1⁺⁺, five (10%) monoallelic carriers (RFC1^+-) and 42 (82%) of wild-type genotype (RFC1^--). No difference was observed in age, sex, cough duration, spirometry, VAS or LCQ scores between RFC1⁺⁺ and RFC1^-- subjects (p>0.05). The symptom of pins and needles was more frequent in RFC1⁺⁺ (n=4, 100%) compared to RFC1^-- (n=12, 33%) (p=0.01). RFC1⁺⁺ participants had impaired sensory action potentials, and one had cerebellar atrophy. RFC1⁺⁺ participants had heightened cough reflex sensitivity to capsaicin, similar to previous CANVAS and RCC studies.

Conclusion: Biallelic RFC1 repeat expansions (RFC1⁺⁺) were present in 8% of RCC patients. RFC1⁺⁺ participants demonstrated features of cough reflex hypersensitivity. RFC1⁺⁺ chronic cough had few identifying features, although symptoms of pins and needles were more common.