OBJECTIVE: Diabetic polyneuropathy is a long-standing microvascular complication of diabetes that affects the postural control and functional mobility of patients. There are other microvascular complications, including pulmonary complications that reduce lung function. Multifactorial Inspiratory Muscle Training (IMT) can act as a home-based technique targeted to affect both these complications. This study aims to determine the effects of IMT on respiratory and functional parameters in diabetic polyneuropathy patients.
METHODS: This is a Pre-Test Post-Test Randomized Controlled Trial (NCT#04947163) with 62 diabetic polyneuropathy patients. Each was randomly assigned to the IMT or sham-IMT group. Both the groups performed OTAGO exercises , with the sham-IMT group performing IMT at 15% of baseline maximal inspiratory pressure (MIP), whereas IMT were trained at 50% of baseline MIP as an initial intensity, which was increased as per the tolerance of patients. Both groups performed training for 12 weeks. The study investigated diaphragmatic strength, pulmonary function, functional capacity through 6MWT, 30s sit to stand test and anterior trunk muscle endurance tested through sit up test as outcome variables. Data was analysed on SPSS v26 at the significance level of 0.0.5.
RESULTS: The IMT group significantly improved diaphragmatic strength, pulmonary function, 6MWT and anterior trunk muscle endurance when compared to the sham-IMT group.
CONCLUSIONS: The study concluded that home-based IMT can improve pulmonary parameters including diaphragmatic strength and lung function as well as functional parameters including functional capacity in patients with diabetic polyneuropathy. The study was registered at ClinicalTrials.gov, NCT#04947163.

BACKGROUND: A minority of school-aged children with asthma have persistent poor control and experience frequent asthma attacks despite maximal prescribed maintenance therapy. These children have higher morbidity and risk of death. The first add-on biologic therapy, omalizumab, a monoclonal antibody that blocks immunoglobulin (Ig)E, was licensed for children with severe asthma in 2005. While omalizumab is an effective treatment, non-response is common. A second biologic, mepolizumab which blocks interleukin 5 and targets eosinophilic inflammation, was licensed in 2018, but the licence was granted by extrapolation of adult clinical trial data to children. This non-inferiority (NI) trial will determine whether mepolizumab is as efficacious as omalizumab in reducing asthma attacks in children with severe therapy resistant asthma (STRA) and refractory difficult asthma (DA).
METHODS: This is an ongoing multicentre 1:1 randomised NI open-label trial of mepolizumab and omalizumab. Up to 150 children and young people (CYP) aged 6-17 years with severe asthma will be recruited from specialist paediatric severe asthma centres in the UK. Prior to randomisation, children will be monitored for medication adherence for up to 16 weeks to determine STRA and refractory DA diagnoses. Current prescribing recommendations of serum IgE and blood eosinophils will not influence eligibility or enrolment. The primary outcome is the 52-week asthma attack rate. Bayesian analysis using clinician-elicited prior distributions will be used to calculate the posterior probability that mepolizumab is not inferior to omalizumab. Secondary outcomes include Composite Asthma Severity Index, Paediatric Asthma Quality of Life Questionnaire, lung function measures (forced expiratory volume in one second (FEV1), bronchodilator reversibility), fractional exhaled nitric oxide, Asthma Control Test (ACT), health outcomes EuroQol 5 Dimension (EQ-5D) and optimal serum IgE and blood eosinophil levels that may predict a response to therapy. These outcomes will be analysed in a frequentist framework using longitudinal models.
BACKGROUND: The study has been approved by the South Central-Berkshire Research Ethics Committee REC Number 19/SC/0634 and had Clinical Trials Authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT 2019-004085-17). All parents/legal guardians will give informed consent for their child to participate in the trial, and CYP will give assent to participate. The results will be published in peer-reviewed journals, presented at international conferences and disseminated via our patient and public involvement partners.
BACKGROUND: ISRCTN12109108; EudraCT Number: 2019-004085-17.

BACKGROUND: This meta-analysis aims to evaluate the agreement and correlation between phase-resolved functional lung MRI (PREFUL MRI) and dynamic contrast-enhanced (DCE) MRI in evaluating perfusion defect percentage (QDP), as well as the agreement between PREFUL MRI and 129Xe MRI in assessing ventilation defect percentage (VDP).
METHODS: A systematic search was conducted in the Medline, Embase and Cochrane Library databases to identify relevant studies comparing QDP and VDP measured by DCE MRI and 129Xe MRI compared with PREFUL MRI. Meta-analytical techniques were applied to calculate the pooled weighted bias, limits of agreement (LOA) and correlation coefficient. The publication bias was assessed using Egger\'s regression test, while heterogeneity was assessed using Cochran\'s Q test and Higgins I2 statistic.
RESULTS: A total of 399 subjects from 10 studies were enrolled. The mean difference and LOA were -2.31% (-8.01% to 3.40%) for QDP and 0.34% (-4.94% to 5.62%) for VDP. The pooled correlations (95% CI) were 0.65 (0.55 to 0.73) for QDP and 0.72 (0.61 to 0.80) for VDP. Furthermore, both QDP and VDP showed a negative correlation with forced expiratory volume in 1 s (FEV1). The pooled correlation between QDP and FEV1 was -0.51 (-0.74 to -0.18), as well as between VDP and FEV1 was -0.60 (-0.73 to -0.44).
CONCLUSIONS: PREFUL MRI is a promising imaging for the assessment of lung function, as it demonstrates satisfactory deviations and LOA when compared with DEC MRI and 129Xe MRI.
UNASSIGNED: CRD42023430847.

This study aimed to investigate the immediate effects of manual therapy (MT) on the respiratory functions of healthy young individuals. The study included 104 participants, consisting of university students (87 females, 17 males, mean age 20.1 ± 2.2). Participants were randomly assigned to the MT (experimental; n = 52) and sham-MT (control; n = 52) groups. The experimental group underwent thoracic manipulations and mobilizations along with diaphragm mobilization. In the control group, the hands were placed on the same regions, but no specific intervention was applied. All participants underwent respiratory function testing before and after the intervention using a portable spirometer (PEF- Peak expiratory flow; FEV 1- Forced expiratory volume in 1 s; FVC- Forced vital capacity and FEV1/FVC- Tiffeneau index). In the experimental group, there was a significant increase in the mean PEF value following MT application from 296.3 ± 110.8 to 316.1 ± 119.1 (p = 0.018). Conversely, the mean PEF value in the control group showed a slight decrease from 337.1 ± 93.3 to 324.5 ± 89.2 (p = 0.002). No significant changes were observed in FVC, FEV1, or FEV1/FVC values pre- and post-intervention in either groups. A single MT session led to a significant improvement in PEF in healthy young individuals. Further research is needed to explore the long-term effects of MT on respiratory functions and its potential implications in clinical practice.Trial registration ClinicalTrials.gov: NCT05934240 (06/07/2023).

OBJECTIVE: To evaluate the effect of short-term inhalational exposure to nanoparticles released during dental composite grinding on oxidative stress and antioxidant capacity markers.
METHODS: Twenty-four healthy volunteers were examined before and after exposure in dental workshop. They spent 76.8 ± 0.7 min in the testing room during grinding of dental nanocomposites. The individual exposure to aerosol particles in each participant´s breathing zones was monitored using a personal nanoparticle sampler (PENS). Exhaled breath condensate (EBC), blood, and urine samples were collected pre- and post-exposure to measure one oxidative stress marker, i.e., thiobarbituric acid reactive substances (TBARS), and two biomarkers of antioxidant capacity, i.e., ferric-reducing antioxidant power (FRAP) and reduced glutathione (GSH) by spectrophotometry. Spirometry and fractional exhaled nitric oxide (FeNO) were used to evaluate the effect of acute inhalational exposure.
RESULTS: Mean mass of dental nanocomposite ground away was 0.88 ± 0.32 g. Average individual doses of respirable particles and nanoparticles measured by PENS were 380 ± 150 and 3.3 ± 1.3 μg, respectively. No significant increase of the post-exposure oxidative stress marker TBARS in EBC and plasma was seen. No decrease in antioxidant capacity biomarkers FRAP and GSH in EBC post-exposure was seen, either. Post-exposure, conjunctival hyperemia was seen in 62.5% volunteers; however, no impairment in spirometry or FeNO results was observed. No correlation of any biomarker measured with individual exposure was found, however, several correlations with interfering factors (age, body mass index, hypertension, dyslipidemia, and environmental pollution parameters) were seen.
CONCLUSIONS: This study, using oxidative stress biomarker and antioxidant capacity biomarkers in biological fluids of volunteers during the grinding of dental nanocomposites did not prove a negative effect of this intense short-term exposure. However, further studies are needed to evaluate oxidative stress in long-term exposure of both stomatologists and patients and diverse populations with varying health statuses.

BACKGROUND: Impaired ventilatory efficiency during exercise is a predictor of mortality in chronic obstructive pulmonary disease. However, little is known about the clinical features and associated factors of impaired ventilatory efficiency in China.
METHODS: We conducted a cross-sectional community-based study in China and collected demographic and clinical information, cardiopulmonary exercise testing, spirometry, and CT data. Impaired ventilatory efficiency was defined by a nadir ventilatory equivalent for CO2 production above the upper limit of normal. Multivariable linear and logistic regression models were used to explore the clinical features and associated factors of impaired ventilatory efficiency.
RESULTS: The final analyses included 941 subjects, 702 (74.6%) of whom had normal ventilatory efficiency and 239 (25.4%) had impaired ventilatory efficiency. Participants with impaired ventilatory efficiency had more chronic respiratory symptoms, poorer lung function and exercise capacity, and more severe emphysema (natural logarithm transformation of the low-attenuation area of the lung with attenuation values below -950 Hounsfield units, logLAA-950: 0.19±0.65 vs -0.28±0.63, p<0.001) and air trapping (logLAA-856: 1.03±0.65 vs 0.68±0.70, p<0.001) than those with normal ventilatory efficiency. Older age (60-69 years, OR 3.10 (95% CI 1.33 to 7.21), p=0.009 and 70-80 years, OR 6.48 (95% CI 2.56 to 16.43), p<0.001 vs 40-49 years) and smoking (former, OR 3.19 (95% CI 1.29 to 7.86), p=0.012; current, OR 4.27 (95% CI 1.78 to 10.24), p=0.001 vs never) were identified as high risk factors of impaired ventilatory efficiency.
CONCLUSIONS: Impaired ventilatory efficiency was associated with poorer respiratory characteristics. Longitudinal studies are warranted to explore the progression of individuals with impaired ventilatory efficiency.

OBJECTIVE: To develop a statistical approach that provides a quantitative index measuring the magnitude of the irregularity of the breathing response to exercise for the diagnosis of dysfunctional breathing.
METHODS: Cross-sectional, retrospective, real-world study.
METHODS: Single-centre study.
METHODS: A population of 209 patients investigated with cardiopulmonary exercise testing in our institution for unexplained or disproportionate exertional dyspnoea between January and July 2022.
METHODS: A novel statistical approach providing a quantitative index-proportional tidal volume variation (PTVV)-was developed to measure the magnitude of the irregularity of the breathing response to exercise.
RESULTS: PTVV provided a reliable statistical readout for the objective assessment of DB with a prediction accuracy of 78% (95% CI: 72 to 83%). The prevalence of DB in the investigated population was high with more than half of the patients affected by moderate-to-severe DB.
CONCLUSIONS: PTVV can easily be implemented in the clinical routine. Our study suggests a possible further simplification for the diagnosis of DB with two objective criteria including PTVV and one single criterion for hyperventilation.

BACKGROUND: Within-breath analysis of oscillometry parameters is a growing research area since it increases sensitivity and specificity to respiratory pathologies and conditions. However, reference equations for these parameters in White adults are lacking and devices using multiple sinusoids or pseudorandom forcing stimuli have been underrepresented in previous studies deriving reference equations. The current study aimed to establish reference ranges for oscillometry parameters, including also the within-breath ones in White adults using multi-sinusoidal oscillations.
METHODS: White adults with normal spirometry, BMI ≤30 kg/m2, without a smoking history, respiratory symptoms, pulmonary or cardiac disease, neurological or neuromuscular disorders, and respiratory tract infections in the previous 4 weeks were eligible for the study. Study subjects underwent oscillometry (multifrequency waveform at 5-11-19 Hz, Resmon PRO FULL, RESTECH Srl, Italy) in 5 centers in Europe and the USA according to international standards. The within-breath and total resistance (R) and reactance (X), the resonance frequency, the area under the X curve, the frequency dependence of R (R5-19), and within-breath changes of X (ΔX) were submitted to lambda-mu-sigma models for deriving reference equations. For each output parameter, an AIC-based stepwise input variable selection procedure was applied.
RESULTS: A total of 144 subjects (age 20.8-86.3 years; height 146-193 cm; BMI 17.42-29.98 kg/m2; 56% females) were included. We derived reference equations for 29 oscillatory parameters. Predicted values for inspiratory and expiratory parameters were similar, while differences were observed for their limits of normality.
CONCLUSIONS: We derived reference equations with narrow confidence intervals for within-breath and whole-breath oscillatory parameters for White adults.

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes.
METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC RESULTS: The final analysis included 1140 participants with preserved spirometry (169 in the variable obstruction group) at baseline. Participants with variable obstruction were older, had lower lung function and had greater severe emphysema and computed tomography-defined air trapping than participants without variable obstruction. Participants with variable obstruction had a significantly increased risk of incident spirometry-defined COPD (relative risk: 3.22, 95% confidence interval 2.23 to 4.64, p <0.001) than those without variable obstruction after adjustment for covariates. These findings remained consistent among both former and current smokers, never smokers, and different variable obstruction types. Additionally, participants with variable obstruction had a faster decline in postbronchodilator FEV1/FVC (2.3±0.5%/year vs 0.9±0.4%/year, mean difference: 1.4 (95% confidence interval 0.5 to 2.3), p=0.002) than participants without variable obstruction after adjustment for covariates.
CONCLUSIONS: The results of our study revealed that variable obstruction can identify individuals who are at risk for the development of COPD and accelerated postbronchodilator FEV1/FVC decline in preserved spirometry.

BACKGROUND: The prevalence, Medicaid use and mortality risk associated with low forced expiratory volume in 1 s (FEV1) among young adults aged 20-35 years are not well understood, despite its potential implications for the development of chronic pulmonary disease and overall prognosis.
METHODS: A retrospective cohort study was conducted among young adults aged 20-35 years old, using data from the National Health and Nutrition Examination Survey, National Death Index and Centers for Medicare & Medicaid Services. Participants were categorised into a low FEV1 group (pre-bronchodilator FEV1%pred <80%) and a normal FEV1 group (FEV1%pred ≥80%). Weighted logistic regression analysis was employed to identify the risk factors associated with low FEV1, while Cox proportional hazard models were used to calculate the hazard ratio (HR) for Medicaid use and the all-cause mortality between the two groups.
RESULTS: A total of 5346 participants aged 20-35 were included in the study, with 329 in the low FEV1 group and 5017 in the normal group. The weighted prevalence of low FEV1 among young adults was 7.1% (95% CI 6.0 to 8.2). Low body mass index (OR=3.06, 95% CI 1.79 to 5.24), doctor-diagnosed asthma (OR=2.25, 1.28 to 3.93), and wheezing or whistling (OR=1.57, 1.06 to 2.33) were identified as independent risk factors for low FEV1. Over a 15-year follow-up, individuals in the low FEV1 group exhibited a higher likelihood of Medicaid use compared with those in the normal group (HR=1.73, 1.07 to 2.79). However, there was no statistically significant increase in the risk of all-cause mortality over a 30-year follow-up period (HR=1.48, 1.00 to 2.19).
CONCLUSIONS: A considerable portion of young adults demonstrated low FEV1 levels, a characteristic that was associated with a higher risk of Medicaid use over a long-term follow-up, yet not linked to an augmented risk of all-cause mortality.