Quantification of breathing irregularity for the diagnosis of dysfunctional breathing using proportional tidal volume variation: a cross-sectional, retrospective real-world study.

OBJECTIVES: 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. DESIGN: Cross-sectional, retrospective, real-world study. SETTING: Single-centre study. PARTICIPANTS: A population of 209 patients investigated with cardiopulmonary exercise testing in our institution for unexplained or disproportionate exertional dyspnoea between January and July 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: 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.

Prevalence, Medicaid use and mortality risk of low FEV1 in adults aged 20-35 years old in the USA: evidence from a population-based retrospective cohort study.

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.

Impaired lung function and lung cancer risk in 461 183 healthy individuals: a cohort study.

BACKGROUND: It has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as preserved ratio impaired spirometry (PRISm) and airflow obstruction (AO), on the incidence and mortality of lung cancer in both general and never-smoker populations remains unclear. We wished to examine the effect of lung function impairments on lung cancer risks. METHODS: This was a retrospective cohort study (1 January 1994 to 31 December 2017) of individuals from a health surveillance programme in Taiwan who underwent baseline spirometry tests at the entry point. PRISm was defined as an FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio >0.7 and FEV1 <0.8, while AO was defined as an FEV1/FVC ratio <0.7. Cox proportional hazards models and cubic spline curves were used to examine the associations between lung function impairments and lung cancer risks. RESULTS: The study included 461,183 individuals, of whom 14.3% had PRISm and 7.9% had AO. A total of 4038 cases of lung cancer and 3314 lung cancer-related deaths were identified during the 23 years of follow-up. Individuals with PRISm and AO exhibited a higher risk of lung cancer incidence and mortality compared with those with normal lung function. The adjusted HRs and 95% CIs were 1.14 (1.03 to 1.26) and 1.23 (1.10 to 1.37) in the overall cohort, and 1.08 (0.93 to 1.24), and 1.23 (1.05 to 1.45) in the never-smoker cohort. The risks of both developing and dying of lung cancer increased with the severity levels of lung function impairments and lower FEV1 values. CONCLUSION: Impaired lung function is associated with increased risks of developing lung cancer and subsequent mortality. The study highlights the importance of considering lung function in lung cancer screening for better candidate selection.

Clinical features and 1-year outcomes of variable obstruction in participants with preserved spirometry: results from the ECOPD study in China.

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

Assessing the causal role of physical activity and leisure sedentary behaviours with chronic obstructive pulmonary disease: a Mendelian randomisation study.

BACKGROUND: Observational studies show that patients with chronic obstructive pulmonary disease (COPD) tend to be sedentary during leisure time. Physical activity (PA) may reduce the risk of COPD, but the causal relationship is unclear. We used a Mendelian randomisation (MR) method to elucidate the association of leisure sedentary behaviours (LSB) and PA with lung function and COPD. METHODS: Data on LSB (n=422 218), PA (n=608 595), COPD (n=299 929) and lung function (n=79 055) were obtained from the large-scale genome-wide association study. Causal inference used inverse variance-weighted, MR-Egger and weighted median. Sensitivity analysis was performed to assess heterogeneity and pleiotropy, and radial MR was used to distinguish outliers. The primary outcome was analysed by multifactorial MR adjusted for daily smoking. RESULTS: The inverse variance weighted analysis indicated that increased moderate-to-vigorous PA (MVPA) is associated with higher levels of forced vital capacity (FVC) (beta=0.27, 95% CI 0.12 to 0.42; p=3.51×10-4). For each increment of 2.8 hours in television watching, the odds of COPD were 2.25 times greater (OR=2.25; 95% CI 1.84 to 2.75; p=2.38×10-15). For early-onset COPD, the odds were 2.11 times greater (OR=2.11; 95% CI 1.56 to 2.85; p=1.06×10-6), and for late-onset COPD, the odds were 2.16 times greater (OR=2.16; 95% CI 1.64 to 2.84; p=3.12×10-8). Similarly, the odds of hospitalisation for COPD were 2.02 times greater with increased television watching (OR=2.02; 95% CI 1.59 to 2.55; p=4.68×10-9). Television watching was associated with lower FVC (beta=-0.19, 95% CI -0.28 to -0.10; p=1.54×10-5) and forced expiratory volume in the 1 s (FEV1) (beta=-0.16, 95% CI -0.25 to -0.08; p=1.21×10-4) levels. The results remained significant after adjustment for smoking. CONCLUSIONS: Our study suggests a potential association with LSB, particularly television watching, is associated with higher odds of COPD and lower indices of lung function as measured continuously, including FEV1 and FVC. Conversely, an increase in MVPA is associated with higher indices of lung function, particularly reflected in increased FVC levels.

Prognostic implication of 1-year decline in diffusing capacity in newly diagnosed idiopathic pulmonary fibrosis.

The progression of idiopathic pulmonary fibrosis (IPF) is assessed through serial monitoring of forced vital capacity (FVC). Currently, data regarding the clinical significance of longitudinal changes in diffusing capacity for carbon monoxide (DLCO) is lacking. We investigated the prognostic implications of a 1-year decline in DLCO in 319 patients newly diagnosed with IPF at a tertiary hospital between January 2010 and December 2020. Changes in FVC and DLCO over the first year after the initial diagnosis were reviewed; a decline in FVC ≥ 5% and DLCO ≥ 10% predicted were considered significant changes. During the first year after diagnosis, a significant decline in FVC and DLCO was observed in 101 (31.7%) and 64 (20.1%) patients, respectively. Multivariable analysis showed that a 1-year decline in FVC ≥ 5% predicted (aHR 2.74, 95% CI 1.88-4.00) and 1-year decline in DLCO ≥ 10% predicted (aHR 2.31, 95% CI 1.47-3.62) were independently associated with a higher risk of subsequent mortality. The prognostic impact of a decline in DLCO remained significant regardless of changes in FVC, presence of emphysema, or radiographic indications of pulmonary hypertension. Therefore, serial monitoring of DLCO should be recommended because it may offer additional prognostic information compared with monitoring of FVC alone.

Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia.

BACKGROUND: The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. PURPOSE: This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. METHODS: This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. RESULTS: A total 150 children (66 females) aged 7.7 years (6.4-9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%-75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P<0.05). The median z scores of FEV1, FEV1/ FVC, and FEF25%-75% among asymptomatic patients were also significantly lower in the severe versus non/mild BPD group (-0.82 vs. 0.09, -1.68 vs. -0.87, -1.59 vs. -0.61, respectively; all P<0.05). The severe BPD group had a higher median (range) CT score than the non/mild BPD group (6 [0-12] vs. 1 [0-10], P<0.001). Prenatal oligohydramnios was strongly associated with both low pulmonary function (FEV1/FVC

Association of high-sensitivity CRP and FEV1%pred: a study on non-pulmonary disease in a population in Beijing, China.

BACKGROUND: No studies have investigated whether high-sensitivity C reactive protein (hsCRP) can be used to predict the forced expiratory volume in 1 s (FEV1)/estimated value of FEV1 (FEV1%pred). This study aimed to assess the association between hsCRP and FEV1%pred in middle-aged and elderly individuals without underlying lung disease. METHODS: The data for this study were obtained from a prospective cohort study that included 1047 middle-aged and elderly citizens from Beijing aged 40-75 years without any evidence of underlying lung diseases with FEV1 >70% after receiving inhalational bronchodilators. The baseline analysis of the participants was performed from 30 May 2018 to 31 October 2018. Restricted cubic spline regression and multivariate linear regression models were used to assess the non-linear association and linear association between hsCRP and FEV1/FEV in 6 s (FEV6) and FEV1%pred, respectively. RESULTS: The hsCRP values of 851 participants were recorded; the values were normal in 713 (83.8%) participants. The remaining 196 participants (18.7%) had missing data. A non-linear association was observed between normal hsCRP values and FEV1/FEV6. hsCRP was linearly and negatively correlated with FEV1%pred, and each 1 SD increase in hsCRP was significantly associated with a 2.4% lower in FEV1%pred. Significantly higher FEV1/FEV6 differences were observed in the female subgroup than those in the male subgroup (p=0.011 for interaction). CONCLUSIONS: hsCRP had a non-linear association with FEV1/FEV6 and a linear negative association with FEV1%pred in individuals with normal hsCRP values. hsCRP can be used to predict FEV1%pred, which can be used to predict the development of chronic obstructive pulmonary disease. hsCRP has a stronger association with lung function in women than that in men. TRIAL REGISTRATION NUMBER: NCT03532893.

Roles of gender and smoking in the associations between urinary phytoestrogens and asthma/wheeze and lung function: evidence from a cross-sectional study.

BACKGROUND: The role of phytoestrogens in asthma/wheeze and lung function remains controversial. Thus, we aimed to examine whether phytoestrogens have beneficial effects on asthma/wheeze, lung function for subgroups and mortality. METHODS: Participants in this study were individuals aged 20 years or older from the National Health and Nutrition Examination Survey. Multivariate logistic regression models were fitted to examine the associations of urinary phytoestrogens with the risk of asthma/wheeze and lung function in individuals with and without asthma/wheeze. Cox proportional hazards regression was used to examine the relationship between urinary phytoestrogens and all-cause mortality. Stratified analyses were conducted based on gender and smoking status. RESULTS: We included 2465 individuals in this study. Enterolactone levels in the highest quartile were associated with a lower risk of asthma than those in the lowest quartile. As compared with the lowest quartile, the highest quartile of enterodiol and enterolactone was associated with a lower risk of wheeze. Significant associations were observed between subtypes of phytoestrogens (equol and enterolactone) and lung function (forced vital capacity (FVC) and forced expiratory volume in 1 s). Besides, FVC was higher in individuals with higher levels of enterodiol. The results were consistent in subpopulations without asthma/wheeze, while the significant difference was not observed in individuals with asthma/wheeze. The stratified analyses revealed that the associations between phytoestrogens and lung function differed by gender and smoking status among subgroups. No significant association was found between urinary phytoestrogens and all-cause mortality. CONCLUSION: In summary, subtypes of phytoestrogens were associated with lower risk of asthma/wheeze and beneficial for lung function improvement in individuals without asthma/wheeze. Furthermore, gender and smoking may interact in the relationship between phytoestrogens and asthma/wheeze, and lung function. Further researches are needed to confirm these associations and explain the results of stratified analyses.

Predicting parameters of airway dynamics generated from inspiratory and expiratory plethysmographic airway loops, differentiating subtypes of chronic obstructive diseases.

BACKGROUND: The plethysmographic shift volume-flow loop (sRaw-loop) measured during tidal breathing allows the determination of several lung function parameters such as the effective specific airway resistance (sReff), calculated from the ratio of the integral of the resistive aerodynamic specific work of breathing (sWOB) and the integral of the corresponding flow-volume loop. However, computing the inspiratory and expiratory areas of the sRaw-loop separately permits the determination of further parameters of airway dynamics. Therefore, we aimed to define the discriminating diagnostic power of the inspiratory and expiratory sWOB (sWOBin, sWOBex), as well as of the inspiratory and expiratory sReff (sReff IN and sReff EX), for discriminating different functional phenotypes of chronic obstructive lung diseases. METHODS: Reference equations were obtained from measurement of different databases, incorporating 194 healthy subjects (35 children and 159 adults), and applied to a collective of 294 patients with chronic lung diseases (16 children with asthma, aged 6-16 years, and 278 adults, aged 17-92 years). For all measurements, the same type of plethysmograph was used (Jaeger Würzburg, Germany). RESULTS: By multilinear modelling, reference equations of sWOBin, sWOBex, sReff IN and sReff EX were derived. Apart from anthropometric indices, additional parameters such as tidal volume (VT), the respiratory drive (P0.1), measured by means of a mouth occlusion pressure measurement 100 ms after inspiration and the mean inspiratory flow (VT/TI) were found to be informative. The statistical approach to define reference equations for parameters of airway dynamics reveals the interrelationship between covariants of the actual breathing pattern and the control of breathing. CONCLUSIONS: We discovered that sWOBin, sWOBex, sReff IN and sReff EX are new discriminating target parameters, that differentiate much better between chronic obstructive diseases and their subtypes, especially between chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO), thus strengthening the concept of precision medicine.

Health risks of exposure to air pollution in areas where coal-fired power plants are located: protocol for a scoping review.

INTRODUCTION: Coal-fired power plants are major sources of air pollution which impact human health. Coal combustion byproducts released into the air include particulate matter, nitrogen oxides and sulphur dioxide. Exposure to fine particulate matter is associated with increased risk of mortality. This scoping review will examine and summarise the current literature on the health risks of exposure to air pollution in areas in which coal-fired power plants exist. METHODS AND ANALYSIS: This scoping review will be conducted according to the Joanna Briggs Institute methodological framework and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Five electronic databases (PubMed, ScienceDirect, Scopus, Web of Science and Google Scholar) will be searched for relevant articles. Studies will be included up until 31 January 2024. There will be no restriction on geographical area. The searches will be limited to studies published in English. Title, abstract, full-text screening and data extraction of relevant articles will be done by two independent reviewers. Discrepancies will be resolved by group discussion. The findings will be presented in tables with a narrative summary. This review will consider epidemiological studies and grey literature that report on the health risks of exposure to air pollution in areas where coal-fired power plants exist. ETHICS AND DISSEMINATION: All data will be collected from published and grey literature. Ethics approval is therefore not required. We will submit our findings for publication in a peer-reviewed journal.

REMOTE-ILD study: Description of the protocol for a multicentre, 12-month randomised controlled trial to assess the clinical and cost-effectiveness of remote monitoring of spirometry and pulse oximetry in patients with interstitial lung disease.

INTRODUCTION: Remote monitoring of home physiological measurements has been proposed as a solution to support patients with chronic diseases as well as facilitating virtual consultations and pandemic preparedness for the future. Daily home spirometry and pulse oximetry have been demonstrated to be safe and acceptable to patients with interstitial lung disease (ILD) but there is currently limited evidence to support its integration into clinical practice. AIM: Our aim is to understand the clinical utility of frequent remote physiological measurements in ILD and the impact of integrating these into clinical practice from a patient, clinical and health economic perspective. METHODS AND ANALYSIS: 132 patients with fibrotic ILD will be recruited and randomised to receive either usual care with remote digital monitoring of home spirometry and pulse oximetry or usual care alone for 12 months. All participants will complete health-related quality of life and experience questionnaires.The primary outcome compares the availability of spirometry measurements within the 2 weeks preceding planned clinic appointments. Secondary outcomes will explore other aspects of clinical and cost-effectiveness of the remote monitoring programme. ETHICS AND DISSEMINATION: The study has been approved by the Camden and Kings Cross Research Ethics Committee (22/LO/0309). All participants will provide informed consent.This study is registered with www. CLINICALTRIALS: gov (NCT05662124).The results of the study will be submitted for presentation at regional and national conferences and submitted for peer-reviewed publication. Reports will be prepared for study participants with the support from our public involvement representatives through the charity Action for Pulmonary Fibrosis.

Association between pulmonary function and rapid kidney function decline: a longitudinal cohort study from CHARLS.

BACKGROUND: Pulmonary function has been reported to be associated with chronic kidney disease. However, the relationship between lung function and rapid kidney function decline remains unclear. METHODS: Participants aged ≥45 years with complete data from the 2011 and 2015 interviews of the China Health and Retirement Longitudinal Study (CHARLS) were included. Lung function, assessed by peak expiratory flow (PEF), and kidney function, assessed by estimated glomerular filtration rate (eGFR), were tested at the baseline and endpoint surveys. Rapid kidney function decline was defined as a decrease in eGFR ≥3 mL/min/1.73 m²/year, and ΔeGFR represented the difference between baseline and endpoint eGFR. Multivariate logistic regression models and linear regression models were employed to evaluate the association between PEF and the risk of rapid eGFR decline, as well as the correlation between PEF and ΔeGFR. RESULTS: A total of 6159 participants were included, with 1157 (18.78%) individuals experiencing a rapid decline in eGFR. After adjusting for potential covariates, higher baseline PEF (Quartile 4 vs Quartile 1, OR=0.95, 95% CI 0.92 to 0.98) and elevated PEF % predicted (OR=0.96, 95% CI 0.94 to 0.99) were found to be associated with a lower risk of rapid eGFR decline. ΔeGFR decreased by 0.217 and 0.124 mL/min/1.73 m² for every 1 L/s increase in baseline PEF (ß (95% CI): -0.217 (-0.393 to -0.042)) and 10% increase in PEF % predicted (ß (95% CI): -0.124 (-0.237 to -0.011)), respectively. During the follow-up period, ΔeGFR decreased as PEF increased over time among participants in Quartile 1 (ß per 1 L/s increase in ΔPEF=-0.581, 95% CI -1.003 to -0.158; ß per 10% increase in ΔPEF % predicted=-0.279, 95% CI -0.515 to -0.043). CONCLUSIONS: Higher PEF was associated with a slower longitudinal eGFR decline in middle-aged and older adults.

Pilot study of paediatric regional lung function assessment via X-ray velocimetry (XV) imaging in children with normal lungs and in children with cystic fibrosis.

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting autosomal recessive genetic condition. It is caused by mutations in the gene that encodes for a chloride and bicarbonate conducting transmembrane channel. X-ray velocimetry (XV) is a novel form of X-ray imaging that can generate lung ventilation data through the breathing cycle. XV technology has been validated in multiple animal models, including the ß-ENaC mouse model of CF lung disease. It has since been assessed in early-phase clinical trials in adult human subjects; however, there is a paucity of data in the paediatric cohort, including in CF. The aim of this pilot study was to investigate the feasibility of performing a single-centre cohort study in paediatric patients with CF and in those with normal lungs to demonstrate the appropriateness of proceeding with further studies of XV in these cohorts. METHODS AND ANALYSIS: This is a cross-sectional, single-centre, pilot study. It will recruit children aged 3-18 years to have XV lung imaging performed, as well as paired pulmonary function testing. The study will aim to recruit 20 children without CF with normal lungs and 20 children with CF. The primary outcome will be the feasibility of recruiting children and performing XV testing. Secondary outcomes will include comparisons between XV and current assessments of pulmonary function and structure. ETHICS AND DISSEMINATION: This project has ethical approval granted by The Women's and Children's Hospital Human Research Ethics Committee (HREC ID 2021/HRE00396). Findings will be disseminated through peer-reviewed publication and conferences. TRIAL REGISTRATION NUMBER: ACTRN12623000109606.

Mycophenolate and azathioprine efficacy in interstitial lung disease: a systematic review and meta-analysis.

OBJECTIVES: Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD. DESIGN: Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded. DATA SYNTHESIS: The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I2 evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design. RESULTS: A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI -4.00 to 9.88, I2=79.3%; %DLco -2.03, 95% CI -4.38 to 0.32, I2=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I2=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DLCO (95% CI 2.05 to 6.79, I2=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence. CONCLUSIONS: There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD. PROSPERO REGISTRATION NUMBER: CRD42023423223.

Impulse oscillometry assessment of respiratory function in pediatric patients with a history of COVID-19.

OBJECTIVE: While coronavirus disease 2019 (COVID-19) is generally considered to exhibit a less severe clinical course in children than in adults, studies have demonstrated that respiratory symptoms can endure for more than 3 months following infection in at least one-third of pediatric cases. The present study evaluates the respiratory functions of children aged 3-15 years within 3-6 months of their recovery from COVID-19 using impulse oscillometry (IOS) and compares them with the values of healthy children. METHODS: Included in this prospective cross-sectional study were 63 patients (patient group) aged 3-15 years who contracted COVID-19 between December 2021 and May 2022, as well as 57 healthy children as a control group, matched for age and sex. The demographic, clinical, and laboratory data of the patients were recorded, and respiratory function was assessed based on airway resistance (zR5, zR20, R5-20) and reactance (zX5, zX20, reactance area [AX], resonant frequency [Fres]) using an IOS device. RESULTS: There were no significant differences in the age, weight, height, and body weight z score values of the two groups (p > .05). While the zR5 and R5-20 levels of the patient group were higher (p = .008 and p < .001, respectively) than those of the controls, the zR20, AX, and Fres values did not differ significantly between the groups (p > .05). The parameters indicating the reactance, including zX5 and zX20, were significantly lower in the patient group than in the control group (p = .028 and p < .001, respectively). CONCLUSION: Total and peripheral airway resistances were found to be elevated in children who had recovered from COVID-19 in the preceding 3-6 months.

Association between serum high-density lipoprotein cholesterol and lung function in adults: three cross-sectional studies from US and Korea National Health and Nutrition Examination Survey.

INTRODUCTION: Cholesterol is an irreplaceable nutrient in pulmonary metabolism; however, studies on high-density lipoprotein cholesterol (HDL-C) levels have shown conflicting results regarding lung function. Therefore, we investigated the association between lung function and HDL-C levels in three cross-sectional studies conducted in the USA and South Korea. METHODS: US National Health and Nutrition Examination Survey (NHANES) III, US NHANES 2007-2012, and Korea National Health and Nutrition Examination Survey (KNHANES) IV-VII performed spirometry and met the American Thoracic Society recommendations. Multiple linear regression models were used to determine the relationship between serum lipid levels and lung function. The models were adjusted for age, sex, household income, body mass index, smoking pack year, use of lipid-lowering medication and race. Serum HDL-C levels were classified into three groups to assess the dose-response relationship according to the guideline from the National Cholesterol Education Program-Adult Treatment Panel III. RESULTS: The adult participants of the KNHANES (n=31 288), NHANES III (n=12 182) and NHANES 2007-2012 (n=9122) were analysed. Multivariate linear regression analysis of the serum cholesterol profiles revealed that only serum HDL-C was associated with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in all three studies. A 1 SD increase in the HDL-C level increased the percent predicted FVC by 0.5%-1.5% p, and the per cent predicted FEV1 by 0.5%-1.7% p. In terms of HDL-C levels, correlations between the HDL-C groups and the per cent predicted FVC and FEV1 showed dose-response relationships. Compared with the normal group, high HDL-C levels increased FVC by 0.75%-1.79% p and FEV1 by 0.55%-1.90% p, while low levels led to 0.74%-2.19% p and 0.86%-2.68% p reductions in FVC and FEV1, respectively. Subgroup analyses revealed weaker associations in females from KNHANES and NHANES III. CONCLUSION: In the three nationwide cross-sectional studies, high HDL-C levels were associated with improved FVC and FEV1. However, future studies are needed to confirm this correlation and elucidate the underlying mechanisms.

Phenotyping the Responses to Systemic Corticosteroids in the Management of Asthma Attacks (PRISMA): protocol for an observational and translational pilot study.

INTRODUCTION: Asthma and its associated exacerbation are heterogeneous. Although severe asthma attacks are systematically prescribed corticosteroids and often antibiotics, little is known about the variability of response to these therapies. Blood eosinophils and fractional exhaled nitric oxide (FeNO) are type 2 inflammation biomarkers that have established mechanistic, prognostic and theragnostic values in chronic asthma, but their utility in acute asthma is unclear. We speculate that the clinical and biological response to those treatments varies according to inflammometry and microbiological test results. METHODS AND ANALYSIS: An observational longitudinal pilot study with multimodal clinical and translational assessments will be performed on 50 physician-diagnosed ≥12-year-old asthmatics presenting with an asthma attack and 12 healthy controls, including blood eosinophil count (venous and point-of-care (POC) capillary blood), FeNO and testing for airway infection (sputum cultures and POC nasopharyngeal swabs). People with asthma will be assessed on day 0 and after a 7-day corticosteroid course, with home monitoring performed in between. The primary analysis will be the change in the forced expiratory volume in 1 s according to type 2 inflammatory status (blood eosinophils ≥0.15×109/L and/or FeNO ≥25 ppb) after treatment. Key secondary analyses will compare changes in symptom scores and the proportion of patients achieving a minimal clinically important difference. Exploratory analyses will assess the relationship between clinical, lung function, inflammatory and microbiome parameters; satisfaction plus reliability indices of POC tests; and sex-gender variability in treatment response. Ultimately, this pilot study will serve to plan a larger trial comparing the clinical and biological response to systemic corticosteroids according to inflammatory biomarkers, offering valuable guidance for more personalised therapeutic strategies in asthma attacks. ETHICS AND DISSEMINATION: The protocol has been approved by the Research Ethics Committee of the CIUSSS de l'Estrie-CHUS, Sherbrooke, Quebec, Canada (#2023-4687). Results will be communicated in an international meeting and submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05870215).

Patient perspectives on home-spirometry in interstitial lung disease: a qualitative co-designed study.

BACKGROUND: Opportunities for home-monitoring are increasing exponentially. Home- spirometry is reproducible and reliable in interstitial lung disease (ILD), yet patients' experiences are not reported. Given the morbidity and mortality associated with ILDs, maintaining health-related quality-of-life is vital. We report our findings from a codesigned, qualitative study capturing the perspectives and experiences of patients using home-spirometry in a UK regional ILD National Health Service England (NHSE) commissioned service. METHODS: Patients eligible for home-spirometry as routine clinical care, able to give consent and able to access a smart phone were invited to participate. In-depth, semistructured interviews were conducted at serial time points (baseline, 1, 3 and 6 months), recorded, transcribed and analysed thematically. RESULTS: We report on the experiences of 10 recruited patients (8 males; median age 66 years, range 50-82 years; 7 diagnosed with idiopathic pulmonary fibrosis, 3 other ILDs) who generally found spirometry convenient and easy to use, but their relationships with forced vital capacity results were complex. Main themes emerging were: (1) anticipated benefits-to identify change, trigger action and aid understanding of condition; (2) needs-clinical oversight and feedback, understanding of results, ownership, need for data and a need 'to know'; (3) emotional impact-worry, reassurance, ambivalence/conflicting feelings, reminder of health issues, indifference; (4) ease of home-spirometry-simplicity, convenience and (5) difficulties with home-spirometry-technical issues, technique, physical effort. CONCLUSION: Home-spirometry has many benefits, but in view of the potential risks to psychological well-being, must be considered on an individual basis. Informed consent and decision-making are essential and should be ongoing, acknowledging potential limitations as well as benefits. Healthcare support is vital.

Fitness checklist model for spontaneous breathing tests in pediatrics.

OBJECTIVE: To evaluate whether a model of a daily fitness checklist for spontaneous breathing tests is able to identify predictive variables of extubation failure in pediatric patients admitted to a Brazilian intensive care unit. METHODS: This was a single-center, cross-sectional study with prospective data collection. The checklist model comprised 20 items and was applied to assess the ability to perform spontaneous breathing tests. RESULTS: The sample consisted of 126 pediatric patients (85 males (67.5%)) on invasive mechanical ventilation, for whom 1,217 daily assessments were applied at the bedside. The weighted total score of the prediction model showed the highest discriminatory power for the spontaneous breathing test, with sensitivity and specificity indices for fitness failure of 89.7% or success of 84.6%. The cutoff point suggested by the checklist was 8, with a probability of extubation failure less than 5%. Failure increased progressively with increasing score, with a maximum probability of predicting extubation failure of 85%. CONCLUSION: The extubation failure rate with the use of this model was within what is acceptable in the literature. The daily checklist model for the spontaneous breathing test was able to identify predictive variables of failure in the extubation process in pediatric patients.