BACKGROUND: Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet.
METHODS: A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts.
RESULTS: Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children.
CONCLUSIONS: A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required.

UNASSIGNED: To determine the association of urinary phthalate metabolites with chronic obstructive pulmonary disease (COPD), airflow obstruction, lung function and respiratory symptoms.
UNASSIGNED: Our study included a total of 2023 individuals aged ≥ 40 years old in the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression was conducted to explore the correlation of eleven urinary phthalate metabolites (MCNP, MCOP, MECPP, MnBP, MCPP, MEP, MEHHP, MEHP, MiBP, MEOHP, and MBzP) with COPD, airflow obstruction and respiratory symptoms. Linear regression analyses were used to evaluate the relationship between urinary phthalate metabolites and lung function.
UNASSIGNED: When compared to the first tertile, the third tertile of MEHHP was associated with the risk of COPD [OR: 2.779; 95% confidence interval (CI): 1.129-6.840; P = 0.026]. Stratified analysis showed that MEHHP increased the risk of COPD by 7.080 times in male participants. Both MCPP and MBzP were positively correlated with the risk of airflow obstruction. The third tertile of MBzP increased the risk of cough by 1.545 (95% CI: 1.030-2.317; P = 0.035) times. Both FEV1 and FVC were negatively associated with MEHHP, MECPP, MnBP, MEP, MiBP and MEOHP.
UNASSIGNED: Higher levels of MEHHP are associated with increased risk of COPD, and lower measures of FEV1 and FVC. MBzP is positively related to airflow obstruction and cough.

BACKGROUND: Childhood asthma is a prevalent condition with potential impact on adult life.
OBJECTIVE: In a 60-year follow-up study of adults with a history of severe childhood asthma, what are the potential differences in characteristics between individuals with persistent asthma and asthma remission in adulthood?
METHODS: Danish adults with a history of childhood asthma and a 4-month stay in at an asthma care facility in Kongsberg, Norway (1950-1979) in childhood were included. Recruitment was done through social media and personal invitation letters. Participants completed questionnaires and underwent spirometry, bronchial provocation, and bronchodilator reversibility and blood tests. Asthma remission was defined as no use of asthma medication and no asthma symptoms within the past 12 months with the remaining participants being classified as having current asthma.
RESULTS: Among 1394 eligible participants, 232 completed the follow-up. Ninety percent had current asthma, of whom 26% reported exacerbations in the past year. Only 16% of all the participants were managed in secondary care. Common comorbidities were allergic rhinitis (60%), hypertension (21%), eczema (16%), and cataract (8%). Compared to participants in remission, participants with persistent asthma had higher total immunoglobulin E (p=0.03), and both lower FEV1%pred (p=0.03), and FEV1/FVC ratio (p<0.001), as well as numerically higher fractional exhaled nitric oxide and blood eosinophil count.
CONCLUSIONS: Our 60-year follow-up study of adults with a history of severe childhood asthma revealed that nine out of ten still had current asthma. Persistent asthma was associated with lower lung function and higher levels of type 2 inflammatory biomarkers compared to those with asthma remission.

BACKGROUND: Data on the impact of liver transplantation (LT) in cystic fibrosis (CF) on lung function and exacerbations are limited. The objective of this study was to summarize the literature on lung function, nutritional status, survival, and complications following LT in people with CF.
METHODS: Three databases were searched until September 2023, to identify the impact of LT in CF. Lung transplant prior to LT and simultaneous liver-lung transplant were excluded. Pooled hazard ratios were calculated using random-effects models.
RESULTS: Thirty studies were included in this review, with 3 and 9 studies included in meta-analyses for nutritional status and lung function, respectively. Eighty-three percent of the studies used data that was more than a decade old. There was a significant increase in percent-predicted forced expiratory volume with mean change of 7.16 % (2.13, 12.19; p = 0.005) one year post-LT. Pulmonary exacerbations decreased in the short-term, however there was no significant change in body mass index (BMI). One-year survival post-LT ranged between 75 and 100 %, while five-year survival was lower at 64-89 %.
CONCLUSIONS: Existing data suggest that LT improves lung function in the short term and does not increase the likelihood of pulmonary exacerbations, despite ongoing immunosuppression in the setting of chronic lung infection.

Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults. The Cr exposure-related metabolomic changes are not well elucidated. This study recruited 608 students from a university in Shandong Province, China in 2019. We used cohort design fitted with linear mixed-effects models to assess the association between blood Cr concentration and lung function. In addition, we performed metabolomic and lipidomic analyses of baseline serum samples (N = 582) using liquid chromatography-mass spectrometry. Two-step statistical analysis (analysis of variance and mixed-linear effect model) was used to evaluate the effect of blood Cr exposure on metabolites. We found that blood Cr was associated with decreased lung function in young adults. Each 2-fold increase in blood Cr concentrations was significantly associated with decreased FEV1 and FVC by 35.26 mL (95 % CI: -60.75, -9.78) and 38.56 mL (95 % CI: -66.60, -10.51), respectively. In the metabolomics analysis, blood Cr exposure was significantly associated with 14 key metabolites. The changed metabolites were mainly enriched in six pathways including lipid metabolism, amino acid metabolism, and cofactor vitamin metabolism. Blood Cr may affect lung function through oxidative stress and inflammation related pathways.

UNASSIGNED: Uneven economic development has led to substantial health inequalities between Chinese provinces. The extent of, and factors underlying, between-province health inequalities have received little attention.
UNASSIGNED: Data from 15,278 respondents in Wave 2 (2013) of the China Health and Retirement Longitudinal Study (CHARLS) were used to investigate inequalities among people aged ≥50 years in five health outcomes between 27 Chinese province-level administrative units. After characterizing the between-province differences and the relevance of province effects, proportional change in variance between unadjusted and adjusted models was calculated to determine the percentage of between-province variance in health outcomes explained by province-level variables including measures of economic development and healthcare availability.
UNASSIGNED: Although province effects explained <10% of overall variance in health outcomes, they underpinned large between-province inequalities among people aged ≥50 years. Gross Regional Product per capita was more important than doctor density in explaining between-province variance in health outcomes, particularly depression symptoms and instrumental activities of daily living impairment.
UNASSIGNED: Policy efforts, including more equal distribution of healthcare personnel, may be warranted to reduce between-province health inequalities.

UNASSIGNED: Impaired lung function has been observed in patients following COVID-19 infection, with studies reporting persistent lung volume and diffusing capacity impairments. Some studies have demonstrated significantly higher small airway resistance in COVID-19 positive cases. This retrospective study aims to examine impulse oscillometry (IOS) data of patients with persistent symptoms after COVID-19 infection, focusing on the relationship between time and symptoms.
UNASSIGNED: The study analyzed data from adult patients with persistent symptoms who underwent IOS testing within and after 84 days from the diagnosis date.
UNASSIGNED: The results showed that patients within 84 days and those between 31 and 84 days had higher small airway resistance values, indicating peripheral airway disease. Patients with dyspnea exhibited higher IOS values compared to those with cough symptoms, suggesting more significant impairment in the peripheral airways.
UNASSIGNED: The study highlights the importance of using comprehensive diagnostic tools like IOS to assess respiratory impairments in post-COVID-19 patients, particularly in the small airways. Understanding the relationship between time and symptoms can provide valuable insights for the treatment of peripheral airway dysfunction in post-COVID-19 patients.

BACKGROUND: The metabolic-status-related mechanisms underlying the deterioration of the lung function in obese asthma have not been completely elucidated.
OBJECTIVE: This study aimed to investigate the basal metabolic rate (BMR) in patients with obese asthma, its association with the lung function, and its mediating role in the impact of obesity on the lung function.
METHODS: A 12-month prospective cohort study (n = 598) was conducted in a real-world setting, comparing clinical, body composition, BMR, and lung function data between patients with obese (n = 282) and non-obese (n = 316) asthma. Path model mediation analyses for the BMR and skeletal muscle mass (SMM) were conducted. We also explored the effects of the BMR on the long-term lung function in patients with asthma.
RESULTS: Patients with obese asthma exhibited greater airway obstruction, with lower FEV1 (1.99 vs. 2.29 L), FVC (3.02 vs. 3.33 L), and FEV1/FVC (65.5 vs. 68.2%) values compared to patients with non-obese asthma. The patients with obese asthma also had higher BMRs (1284.27 vs. 1210.08 kcal/d) and SMM (23.53 vs. 22.10 kg). Both the BMR and SMM mediated the relationship between obesity and the lung function spirometers (FEV1, %FEV1, FVC, %FVC, and FEV1/FVC). A higher BMR or SMM was associated with better long-term lung function.
CONCLUSIONS: Our study highlights the significance of the BMR and SMM in mediating the relationship between obesity and spirometry in patients with asthma, and in determining the long-term lung function. Interventions for obese asthma should focus not only on reducing adiposity but also on maintaining a high BMR.

OBJECTIVE: There is a major epidemic of obesity, and many obese patients suffer from respiratory symptoms and disease. However, limited research explores the associations between abdominal obesity and lung function indices, yielding mixed results. This study aims to analyze the association between waist circumference (WC), an easily measurable marker of abdominal obesity, and lung function parameters in middle-aged and older adults using the National Health and Nutrition Examination Survey (NHANES).
METHODS: This study utilized data obtained from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012, with a total sample size of 6089 individuals. A weighted multiple regression analysis was conducted to assess the relationship between WC and three pulmonary function parameters. Additionally, a weighted generalized additive model and smooth curve fitting were applied to capture any potential nonlinear relationship within this association.
RESULTS: After considering all confounding variables, it was observed that for each unit increase in WC, in males, Forced Vital Capacity (FVC) increased by 23.687 ml, Forced Expiratory Volume in one second (FEV1) increased by 12.029 ml, and the FEV1/FVC ratio decreased by 0.140%. In females, an increase in waist circumference by one unit resulted in an FVC increase of 6.583 ml and an FEV1 increase of 4.453 ml. In the overall population, each unit increase in waist circumference led to a FVC increase of 12.014 ml, an FEV1 increase of 6.557 ml, and a decrease in the FEV1/FVC ratio by 0.076%. By constructing a smooth curve, we identified a positive correlation between waist circumference and FVC and FEV1. Conversely, there was a negative correlation between waist circumference and the FEV1/FVC ratio.
CONCLUSIONS: Our findings indicate that in the fully adjusted model, waist circumference, independent of BMI, positively correlates with FVC and FEV1 while exhibiting a negative correlation with FEV1/FVC among middle-aged and older adults in the United States. These results underscore the importance of considering abdominal obesity as a potential factor influencing lung function in American middle-aged and older adults.

BACKGROUND: Harmine has many pharmacological activities and has been found to significantly inhibit the fibrosis of keloid fibroblasts. DNA damage repair (DDR) is essential to prevent fibrosis. This study aimed to investigate the effects of harmine on pulmonary fibrosis and its underlying mechanisms.
METHODS: Bleomycin and TGF-β1 were used to construct pulmonary fibrosis models in vivo and in vitro, then treated with harmine to explore harmine\'s effects in treating experimental pulmonary fibrosis and its related mechanisms. Then, RNA sequencing was applied to investigate further the crucial DDR-related genes and drug targets of harmine against pulmonary fibrosis. Finally, the expression levels of DDR-related genes were verified by real-time quantitative PCR (RT-qPCR) and western blot.
RESULTS: Our in vivo experiments showed that harmine treatment could improve weight loss and lung function and reduce tissue fibrosis in mice with pulmonary fibrosis. The results confirmed that harmine could inhibit the viability and migration of TGF-β1-induced MRC-5 cells, induce their apoptosis, and suppress the F-actin expression, suggesting that harmine could suppress the phenotypic transition from lung fibroblasts to lung myoblasts. In addition, RNA sequencing identified 1692 differential expressed genes (DEGs), and 10 DDR-related genes were screened as critical DDR-related genes. RT-qPCR and western blotting showed that harmine could down-regulate the expression of CHEK1, ERCC1, ERCC4, POLD1, RAD51, RPA1, TOP1, and TP53, while up-regulate FEN1, H2AX and GADD45α expression.
CONCLUSIONS: Harmine may inhibit pulmonary fibrosis by regulating DDR-related genes and activating the TP53-Gadd45α pathway.