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UNASSIGNED: To systematically assess decline in respiratory measures in amyotrophic lateral sclerosis (ALS) and to examine the impact of sex, disease onset type and baseline morbidity on progression.
UNASSIGNED: The REVEALS study (Registry of Endpoints and Validated Experiences in ALS) was conducted between April 2018 and February 2021 in six European ALS centers. Slow and forced vital capacity (S/FVC), sniff nasal inspiratory pressure (SNIP), peak cough flow, amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R), and respiratory morbidity were collected. Data were analyzed using a Bayesian multiple outcomes random effects model.
UNASSIGNED: Two hundred and eighty participants had a median of three assessments (IQR 2.0, 5.0) over a median of 8 months (IQR 2.3, 14.1). There were 974 data collection timepoints. Differences in respiratory measures and rates of decline between disease-onset and sex subgroups were identified. Females had lower scores in all respiratory measures and females with bulbar onset ALS had faster decline compared with other sub-groups. These differences were not detected by the ALSFRS-r respiratory subscale. Dyspnea, orthopnea, and a higher King\'s stage at baseline were associated with lower respiratory scores throughout follow-up, while having a regular productive cough at baseline was associated with lower peak cough flow scores.
UNASSIGNED: Respiratory function declines more quickly in females with ALS compared with males when measured by FVC, SVC, SNIP, or PCF, but not the ALSFRS-R respiratory sub-score. Higher baseline King\'s staging and the presence of clinical respiratory symptoms at baseline were associated with worse respiratory function. The ALSFRS-R respiratory sub-score is poorly correlated with objective respiratory measurements.

BACKGROUND: Lung function in early adulthood is associated with subsequent adverse health outcomes.
OBJECTIVE: To ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function.
METHODS: Using latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). We used multinomial logistic regression models to investigate early-life predictors of the derived trajectories. We then ascertained the extent of the association between the derived FEV1/FVC trajectories and blood pressure and echocardiographic markers of increased cardiovascular risk and stroke in ~3200 participants at age 24 years in one of our cohorts.
RESULTS: We identified four FEV1/FVC trajectories with strikingly similar latent profiles across cohorts (pooled N=6377): above average (49.5%); average (38.3%); below average (10.6%); and persistently low (1.7%). Male sex, wheeze, asthma diagnosis/medication and allergic sensitisation were associated with trajectories with diminished lung function in all cohorts. We found evidence of an increase in cardiovascular risk markers ascertained by echocardiography (including left ventricular mass indexed to height and carotid intima-media thickness) with decreasing FEV1/FVC (with p values for the mean crude effects per-trajectory ranging from 0.10 to p<0.001). In this analysis, we considered trajectories as a pseudo-continuous variable; we confirmed the assumption of linearity in all the regression models.
CONCLUSIONS: Childhood lung function trajectories may serve as predictors in the development of not only future lung disease, but also the cardiovascular disease and multimorbidity in adulthood.

BACKGROUND: Methods used to assess ventilation heterogeneity through inert gas washout have been standardised and showed high sensitivity in diagnosing many respiratory diseases. We hypothesised that nitrogen single or multiple breath washout tests, respectively nitrogen single breath washout (N2SBW) and nitrogen multiple breath washout (N2MBW), may be pathological in patients with clinical suspicion of asthma but normal spirometry. Our aim was to assess whether N2SBW and N2MBW are associated with methacholine challenge test (MCT) results in this population. We also postulated that an alteration in SIII at N2SBW could be detected before the 20% fall of forced expiratory volume in the first second (FEV1) in MCT.
METHODS: This prospective, observational, single-centre study included patients with suspicion of asthma with normal spirometry. Patients completed questionnaires on symptoms and health-related quality-of-life and underwent the following lung function tests: N2SBW (SIII), N2MBW (Lung clearance index (LCI), Scond, Sacin), MCT (FEV1 and sGeff) as well as N2SBW between each methacholine dose.
RESULTS: 182 patients were screened and 106 were included in the study, with mean age of 41.8±14 years. The majority were never-smokers (58%) and women (61%). MCT was abnormal in 48% of participants, N2SBW was pathological in 10.6% at baseline and N2MBW abnormality ranged widely (LCI 81%, Scond 18%, Sacin 43%). The dose response rate of the MCT showed weak to moderate correlation with the subsequent N2SBW measurements during the provocation phases (ρ 0.34-0.50) but no correlation with N2MBW.
CONCLUSIONS: Both MCT and N2 washout tests are frequently pathological in patients with suspicion of asthma with normal spirometry. The weak association and lack of concordance across the tests highlight that they reflect different but not interchangeable pathological pathways of the disease.

OBJECTIVE: This study aimed to systematically review the psychometric properties of outcome measures that assess dysfunctional breathing (DB) in adults.
METHODS: Studies on developing and evaluating measurement properties to assess DB were included. The study investigated the empirical research published between 1990 and February 2022, with an updated search in May 2023 in the Cochrane Library database of systematic reviews and the Cochrane Central Register of Controlled Trials, the Ovid Medline (full), the Ovid Excerta Medica Database, the Ovid allied and complementary medicines database, the Ebscohost Cumulative Index to Nursing and Allied Health Literature and the Physiotherapy Evidence Database. The included studies\' methodological quality was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias checklist. Data analysis and synthesis followed the COSMIN methodology for reviews of outcome measurement instruments.
RESULTS: Sixteen studies met the inclusion criteria, and 10 outcome measures were identified. The psychometric properties of these outcome measures were evaluated using COSMIN. The Nijmegen Questionnaire (NQ) is the only outcome measure with \'sufficient\' ratings for content validity, internal consistency, reliability and construct validity. All other outcome measures did not report characteristics of content validity in the patients\' group.
CONCLUSIONS: The NQ showed high-quality evidence for validity and reliability in assessing DB. Our review suggests that using NQ to evaluate DB in people with bronchial asthma and hyperventilation syndrome is helpful. Further evaluation of the psychometric properties is needed for the remaining outcome measures before considering them for clinical use.
UNASSIGNED: CRD42021274960.

BACKGROUND: Cardiovascular comorbidities are increasingly being recognised in early stages of chronic obstructive pulmonary disease (COPD) yet complete cardiorespiratory functional assessments of individuals with mild COPD or presenting with COPD risk factors are lacking. This paper reports on the effectiveness of the cardiocirculatory-limb muscles oxygen delivery and utilisation axis in smokers exhibiting no, or mild to moderate degrees of airflow obstruction using standardised cardiopulmonary exercise testing (CPET).
METHODS: Post-bronchodilator spirometry was used to classify participants as \'ever smokers without\' (n=88), with \'mild\' (n=63) or \'mild-moderate\' COPD (n=56). All underwent CPET with continuous concurrent monitoring of oxygen uptake (V\'O2) and of bioimpedance cardiac output (Qc) enabling computation of arteriovenous differences (a-vO2). Mean values of Qc and a-vO2 were mapped across set ranges of V\'O2 and Qc isolines to allow for meaningful group comparisons, at same metabolic and circulatory requirements.
RESULTS: Peak exercise capacity was significantly reduced in the \'mild-moderate COPD\' as compared with the two other groups who showed similar pulmonary function and exercise capacity. Self-reported cardiovascular and skeletal muscle comorbidities were not different between groups, yet disease impact and exercise intolerance scores were three times higher in the \'mild-moderate COPD\' compared with the other groups. Mapping of exercise Qc and a-vO2 also showed a leftward shift of values in this group, indicative of a deficit in peripheral O2 extraction even for submaximal exercise demands. Concurrent with lung hyperinflation, a distinctive blunting of exercise stroke volume expansion was also observed in this group.
CONCLUSIONS: Contrary to the traditional view that cardiovascular complications were the hallmark of advanced disease, this study of early COPD spectrum showed a reduced exercise O2 delivery and utilisation in individuals meeting spirometry criteria for stage II COPD. These findings reinforce the preventive clinical management approach to preserve peripheral muscle circulatory and oxidative capacities.

We conducted a prospective single-centre cohort study of 104 multi-ethnic severe COVID-19 survivors from the first wave of the pandemic 15 months after hospitalisation. Of those who were assessed at 4 and 15 months, improvement of ground glass opacities correlated with worsened fibrotic reticulations. Despite a high prevalence of fibrotic patterns (64%), pulmonary function, grip strength, 6 min walk distance and frailty normalised. Overall, dyspnoea, cough and exhaustion did not improve and were not correlated with pulmonary function or radiographic fibrosis at 15 months, suggesting non-respiratory aetiologies. Monitoring persistent, and often subclinical, fibrotic interstitial abnormalities will be needed to determine their potential for future progression.

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