Complications of chest wall around malignant tumors: differences based on reconstruction strategy.

BACKGROUND: Malignant chest wall tumors need to be excised with wide resection to ensure tumor free margins, and the reconstruction method should be selected according to the depth and dimensions of the tumor. Vascularized tissue is needed to cover the superficial soft tissue defect or bone tissue defect. This study evaluated differences in complications according to reconstruction strategy. METHODS: Forty-five patients with 52 operations for resection of malignant tumors in the chest wall were retrospectively reviewed. Patients were categorized as having superficial tumors, comprising Group A with simple closure for small soft tissue defects and Group B with flap coverage for wide soft tissue defects, or deep tumors, comprising Group C with full-thickness resection with or without mesh reconstruction and Group D with full-thickness resection covered by flap with or without polymethyl methacrylate. Complications were evaluated for the 52 operations based on reconstruction strategy then risk factors for surgical and respiratory complications were elucidated. RESULTS: Total local recurrence-free survival rates in 45 patients who received first operation were 83.9% at 5 years and 70.6% at 10 years. The surgical complication rate was 11.5% (6/52), occurring only in cases with deep tumors, predominantly from Group D. Operations needing chest wall reconstruction (p = 0.0016) and flap transfer (p = 0.0112) were significantly associated with the incidence of complications. Operations involving complications showed significantly larger tumors, wider areas of bony chest wall resection and greater volumes of bleeding (p < 0.005). Flap transfer was the only significant predictor identified from multivariate analysis (OR: 10.8, 95%CI: 1.05-111; p = 0.0456). The respiratory complication rate was 13.5% (7/52), occurring with superficial and deep tumors, particularly Groups B and D. Flap transfer was significantly associated with the incidence of respiratory complications (p < 0.0005). Cases in the group with respiratory complications were older, more frequently had a history of smoking, had lower FEV1.0% and had a wider area of skin resected compared to cases in the group without respiratory complications (p < 0.05). Preoperative FEV1.0% was the only significant predictor identified from multivariate analysis (OR: 0.814, 95%CI: 0.693-0.957; p = 0.0126). CONCLUSIONS: Surgical complications were more frequent in Group D and after operations involving flap transfer. Severe preoperative FEV1.0% was associated with respiratory complications even in cases of superficial tumors with flap transfer.

Model-based comparisons of post-treatment free IgE and FEV1 between omalizumab asthma dosing tables in the United States and European Union.

AIMS: Omalizumab is an anti-immunoglobulin E (IgE) monoclonal antibody that was first approved by the United States (US) Food and Drug Administration (FDA) for the treatment of allergic asthma in 2003. The pivotal trials supporting the initial approval of omalizumab used dosing determined by patient's baseline IgE and body weight, with the goal of reducing the mean free IgE level to approximately 25 ng/mL or less. While the underlying parameters supporting the dosing table remained the same, subsequent studies and analyses have resulted in approved alternative versions of the dosing table, including the European Union (EU) asthma dosing table, which differs in weight bands and maximum allowable baseline IgE and omalizumab dose. In this study, we leveraged modelling and simulation approaches to predict and compare the free IgE reduction and forced expiratory volume in 1 second (FEV1) improvement with omalizumab dosing based on the US and EU asthma dosing tables. METHODS: Previously established population pharmacokinetic-IgE and IgE-FEV1 models were used to predict and compare post-treatment free IgE and FEV1 based on the US and EU dosing tables. Clinical trial simulations (with virtual asthma populations) and Monte Carlo simulations were performed to provide both breadth and depth in the comparisons. RESULTS: The US and EU asthma dosing tables were predicted to result in generally comparable free IgE suppression and FEV1 improvement. CONCLUSIONS: Despite the similar free IgE and FEV1 outcomes from simulations, this has not been clinically validated with respect to the registrational endpoint of reduction in annualized asthma exacerbations.

Comparison of race-specific and race-neutral GLI spirometric reference equations with an Indian reference equation.

BACKGROUND: Despite the increasing popularity and use of Global Lung Function Initiative (GLI) spirometric reference equations, the appropriateness of the race-specific and race-neutral GLI spirometric reference models among the Indian population has not been systematically investigated. METHODS: In this cross-sectional analysis, we used spirometric measurements of 1123 healthy Indian adults (≥18 years of age). We computed reference values and z-scores for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC from race-specific and race-neutral GLI reference equations as well as from a widely used Indian reference equation. We studied heterogeneity between GLI equations and the Indian equations using Bland-Altman analysis, and the differences between the reference and observed values were compared using the Friedman test. RESULTS: In Bland-Altman analysis, significant heterogeneity in FVC and FEV1 between race-specific and Indian equations was observed (bias: 10.4 % and 14.1 %, respectively), with less bias for FEV1/FVC (3.76 %). The race-neutral equations showed almost similar bias (9.8 %, 13.8 %, and 3.8 % for FVC, FEV1, and FEV1/FVC, respectively). Median differences in race-specific reference values from observed values for FVC and FEV1 were 0.49L and 0.44L, respectively, decreasing slightly with race-neutral equations (0.46L and 0.43L) whereas Indian models showed minimal differences (FVC: 0.10L, FEV1: 0.05L). Z-scores for FVC and FEV1 were significantly different between race-specific and race-neutral GLI equations, and both differed from Indian equations. CONCLUSION: Both race-specific and race-neutral GLI reference equations are significantly different from the Indian equations, which underscores the importance of determining the suitability of global reference models before being used indiscriminately.

Pollution exposure in the 1st 3 months post transplant is associated with lower baseline FEV1 and higher CLAD risk.

BACKGROUND: Exposure to air pollution post lung transplant has been shown to decrease graft and patient survival. This study examines the impact of air pollution exposure in the first 3 months post-transplant on baseline (i.e. highest) forced expiratory volume in 1s (FEV1) achieved and development of chronic lung allograft dysfunction (CLAD). METHODS: Double-lung transplant recipients (n=82) were prospectively enrolled for comprehensive indoor and personal environmental monitoring at 6- and 12-weeks post-transplant and followed for >4 years. Associations between clinical and exposure variables were investigated using an exposomics approach followed by analysis with a Cox Proportional Hazards model. Multivariable analyses were used to examine the impact of air pollution on baseline % predicted FEV1 (defined as the average of the 2 highest values achieved post-transplant) and risk of CLAD. RESULTS: Multivariable analysis revealed a significant inverse relationship between personal black carbon (BC) levels and baseline % FEV1. The multivariable model indicated that patients with higher-than-median exposure to BC (>350 ng/m3) attained a baseline % FEV1 that was 8.8% lower than those with lower-than-median BC exposure (p = 0.019). Cox proportional hazards model analysis revealed that patients with high personal BC exposure had a 2.4 times higher hazard risk for CLAD than patients with low BC exposure (p = 0.045). CONCLUSIONS: Higher personal BC levels during the first 3 months post-transplant decreases baseline FEV1 and doubles the risk of CLAD. Strategies to reduce BC exposure early following lung transplant may help improve lung function and long-term outcomes.

The impact of inflammatory cells on lung function in asthmatics in a cross sectional retrospect study.

Background: Limited data exists on the impact of inflammatory cells and clinical characteristics on lung function in individuals with asthma. Objective: The objective is to examine the correlation between increased inflammatory cells, asthma symptoms, and lung function in patients with asthma in a clinical setting. Methods: A retrospective cohort study was conducted on 234 individuals suspected of having asthma in Xian, China between January 2008 and December 2021. Of those, 143 patients with complete clinical feature and lung function data were enrolled to examine the relationship between increased inflammatory cells, asthma symptoms, and lung function. Basic characteristics, blood eosinophil count, blood neutrophil count, blood platelet count, blood C-reactive protein (CRP), and comprehensive lung function analysis were evaluated at each inpatient for the 143 adult asthmatics. The association between inflammatory cells and clinical parameters with pulmonary function was compared. Results: The results of the study showed that individuals in the alcohol intake group had elevated blood eosinophil count compared to those in the non-alcohol intake group (P = 0.024). Long-acting inhaled beta 2 agonists and antibiotic therapy were associated with lower blood eosinophil count (P = 0.021 and P = 0.049, respectively) compared to other therapy. There was a independent association between blood eosinophil counts and FEV1 pre- and post-therapy in asthma but there was a markedly correlation between blood eosinophil counts and FEV1/FVC pre-and post-therapy in Asthma (P = 0.007). Blood neutrophil counts were inversely correlated with FEV1/FVC after treatment (P = 0.032). Night onset in asthma was positively correlated with blood neutrophil counts, while fever was negatively correlated with blood CRP (P = 0.028). Platelet counts >300 × 109/L after treatment were significantly associated with a decline in FEV (<0.001) in patients with asthma. Elevated blood eosinophil count was independently associated with clinical features in asthma. Conclusions: Based on the study's findings, there is a significant decline in FEV1/FVC among individuals with elevated blood eosinophil count, both pre- and post-bronchodilator while there was a independent relationship between blood eosinophil counts and FEV1 pre-and post-therapy in asthma. This suggests that increased levels of eosinophils may independently associated contribute to reduced lung function in asthma patients.

Associations of Cardiorespiratory Fitness and Muscular Endurance Fitness With Pulmonary Function in Physically Active Young Adults.

RATIONALE: While the beneficial effects of physical fitness on general health are well-documented, the specific relationship between different types of physical fitness, particularly cardiorespiratory fitness (CRF) and muscular endurance fitness (MEF), and lung function in physically active young adults remains less explored. OBJECTIVE: This study investigated the relationship between CRF and MEF, and their correlation with lung function in physically active young adults. METHODS: This cross-sectional study involved a cohort of 1227 physically active young adults without lung diseases. Lung function was assessed using FEV1, FVC, and FEV1/FVC measurements. The 3000-m run was used to assess CRF, and the 2-min push-up and sit-up tests were used to assess MEF. Multivariable linear regression analysis was used to evaluate the relationships between these fitness measures and lung function, adjusting for potential covariates. RESULTS: Enhanced CRF was associated with superior FEV1 and FVC after adjusting for covariates (ß=-.078, p=.015 for FEV1; ß=-.086, p=.009 for FVC). Push-ups were positively associated with FEV1 (ß=.102, p=.014), but not with FVC. In contrast, sit-ups showed no significant correlation with lung function in the fully adjusted model. CONCLUSION: The study demonstrated a clear association between improved physical fitness and better lung function in physically active young adults, with various exercises showing distinct associations with lung metrics. Notably, push-ups were particularly associated with higher FEV1. A future prospective study is necessary to determine whether routine exercises, such as push-ups, might lead to greater lung function.

Dupilumab 200 mg was efficacious in children (6-11 years) with moderate-to-severe asthma for up to 2 years: EXCURSION open-label extension study.

BACKGROUND: The phase 3 VOYAGE (NCT02948959) and open-label extension EXCURSION (NCT03560466) studies evaluated dupilumab in children (6-11 years) with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed the efficacy and safety of add-on dupilumab 200 mg every 2 weeks (q2w), the largest dose cohort in both studies, in children from VOYAGE who participated in EXCURSION. METHODS: Annualized rate of severe asthma exacerbations (AERs), change in prebronchodilator percent predicted forced expiratory volume in 1 s (ppFEV1), and treatment-emergent adverse events were assessed in children with moderate-to-severe asthma who received dupilumab 200 mg q2w in VOYAGE and EXCURSION (dupilumab/dupilumab arm) and those who received placebo in VOYAGE and dupilumab 200 mg q2w in EXCURSION (placebo/dupilumab arm). These endpoints were also assessed in children with moderate-to-severe type 2 asthma (defined as blood eosinophil count ≥150 cells/µL or FeNO ≥20 ppb at the parent study baseline [PSBL]). RESULTS: In the overall population, dupilumab reduced AER and improved prebronchodilator ppFEV1 in the dupilumab/dupilumab arm (n = 158) for up to 2 years. Children receiving placebo/dupilumab (n = 85) showed similar reductions after initiation of dupilumab 200 mg q2w in EXCURSION. Similar results were observed for children with type 2 asthma at PSBL. The safety profile was consistent with the known safety profile of dupilumab. CONCLUSION: In children (6-11 years) with uncontrolled moderate-to-severe type 2 asthma, dupilumab 200 mg reduced exacerbation rates and improved lung function for up to 2 years and showed safety consistent with the known dupilumab safety profile.

Longitudinal lung function trajectories in response to azithromycin therapy for chronic lung disease in children with HIV infection: a secondary analysis of the BREATHE trial.

BACKGROUND: Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function. METHODS: The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point. RESULTS: Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8-8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV1 z-score was - 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load. CONCLUSION: There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function. TRIAL REGISTRATION: ClinicalTrials.gov NCT02426112. First registered on 24/04/2015.

Factors associated with pulmonary function decline of patients in the cystic fibrosis registry of Turkey: A retrospective cohort study.

BACKGROUND: The decline in pulmonary function is a predictor of disease progression in patients with cystic fibrosis (CF). This study aimed to determine the decline rate of percent predicted forced expiratory volume in 1 s (ppFEV1) based on the data of the CF Registry of Turkey. The secondary aim was to investigate the risk factors related to the decline in ppFEV1. METHODS: A retrospective cohort study of CF patients over 6 years old, with pulmonary function data over at least 2 years of follow-up was extracted from the national CF registry for years 2017-2019. Patients were classified according to disease severity and age groups. Multivariate analysis was used to predict the decline in ppFEV1 and to investigate the associated risk factors. RESULTS: A total of 1722 pulmonary function test results were available from 574 patients over the study period. Mean diagnostic age was older and weight for age, height for age, and body mass index z scores were significantly lower in the group of ppFEV1 < 40, while chronic Pseudomonas aeruginosa (p < .001) and mucoid P. aeruginosa colonization (p < .001) were significantly higher in this group (p < .001). Overall mean annual ppFEV1 decline was -0.97% (95% confidence interval [CI] = -0.02 to -1.92%). The mean change of ppFEV1 was significantly higher in the group with ppFEV1 ≥ 70 compared with the other (ppFEV1 < 40 and ppFEV1: 40-69) two groups (p = .004). Chronic P. aeruginosa colonization (odds ratio [OR] = 1.79 95% CI = 1.26-2.54; p = .01) and initial ppFEV1 ≥ 70 (OR = 2.98 95% CI = 1.06-8.36), p = .038) were associated with significant ppFEV1 decline in the whole cohort. CONCLUSIONS: This data analysis recommends close follow-up of patients with normal initial ppFEV1 levels at baseline; advocates for early interventions for P. aeruginosa; and underlines the importance of nutritional interventions to slow down lung disease progression.

The effect of Lactobacillus reuteri on pulmonary function test and growth of cystic fibrosis patients.

INTRODUCTION: Cystic fibrosis (CF) patients frequently experience gut microbiota dysbiosis. Probiotic supplementation is a potential therapeutic approach to modify gut microbiota and improve CF management through the gut-lung axis. The aim of this study was to investigate the effect of Lactobacillus reuteri supplementation on pulmonary function test, respiratory symptoms and growth in CF patients. METHODS: A randomized, placebo-controlled clinical trial was carried out on 40 children with CF aged from 6 to 20 years. Participants were designated to receive either L. reuteri or placebo daily for 4 months. Pulmonary function tests, weight, height and body mass index (BMI) z-scores were measured pre and post treatment. RESULTS: The median baseline BMI of the patients was 16.28 kg m-2. A significant change in the probiotic group's BMI z-score after the study period was observed (P = 0.034) but not for weight and height z-scores (P > 0.05). After treatment, Pseudomonas aeruginosa grew in sputum cultures of seven in the placebo and one patient in the intervention group (P = 0.03) while at baseline it grew in the sputum of four patients in each group. There was no significant difference in forced expiratory volume in the first second, forced expiratory flow at 25-75% or forced vital capacity change between the two groups after the treatment period (P > 0.05). Additionally, no significant differences were found in pulmonary exacerbations, hospitalization frequencies or COVID-19 infection between the two groups during the study (P > 0.05). CONCLUSION: The results suggest that L. reuteri supplementation may impact the growth of severely malnourished CF patients. Furthermore, it may be concluded that this strain might reduce P. aeruginosa in the sputum culture of CF patients. © 2024 Society of Chemical Industry.

Hospital-treated infectious diseases, infection burden and risk of lung cancer: an observational and Mendelian randomisation study.

BACKGROUND: Although infections play a role in the development of lung cancer, the longitudinal association between infection and the risk of lung cancer is disputed and data relating to pathogen types and infection sites is sparse. RESEARCH QUESTION: How do infections impact subsequent lung cancer risk and whether the impact is limited to specific microbes rather than infection burden? METHODS: We ascertained 900+ infectious diseases from the UK Biobank study. Short- and long-term effect of infections was assessed using time-varying Cox proportional hazard models. The analysis was repeated, excluding patients with concurrent multi-pathogen infections or outcomes within the ten years after initial hospitalization for the index infection. Life table was used to estimate years of life lost from lung cancer. Infection burden was defined as the sum of the number of infection episodes over time and co-occurring infections. The genome-wide association studies (GWAS) used in two-sample Mendelian randomization (MR) were obtained from mostly European ancestry. RESULTS: Hospital-treated infectious disease was associated with a greater risk of lung cancer (adjusted HR [aHR] 1.79 [95% CI 1.74-1.83]). aHRs for lung cancer ranged from 1.39 to 2.82 across pathogen types. The impact of lower respiratory tract infections (LRTIs) on lung cancer was the strongest, with an aHR of 3.22 [95% CI 2.64-3.92], while the aHR for extra-LRTIs was 1.29 [1.16-1.44]). A dose-response association was observed between infection burden and lung cancer risk across different FEV1% predicted (p-trend <0.001). Multiple infections led to a significant life lost from lung cancer at the age of 50. MR analysis reaffirmed the causal association. INTERPRETATION: Both observational and genetic analyses suggested that infectious diseases could increase the risk of lung cancer. The dual perspective on the LRTIs and extra-LRTIs impacts may inform lung cancer preventive strategies.

The predictive role of lung clearance index on FEV1 decline in cystic fibrosis.

BACKGROUND: The lung clearance index (LCI) is a sensitive lung function index that is used to detect early lung disease changes in children with cystic fibrosis (CF). This study aimed to define the predictive role of baseline LCI, along with other potential factors on the change in forced expiratory volume in one second (FEV1) during one-year follow-up in CF patients who had a percent predicted (pp) FEV1≥80. METHODS: LCI was concurrently performed on 57 CF patients who had ppFEV1 ≥80 at month zero. The ppFEV1 decline was evaluated prospectively during the one year follow up. The primary outcome of ppFEV1 decline in the study group in one year was dichotomized according to the median value for the decline in ppFEV1, which was 3.7. The LCI value predicting ppFEV1 decline at the end of one year was calculated with receiver operating characteristic curve analysis. Regression analysis was performed. Furthermore, a decision tree was constructed using classification and regression tree methods to better define the potential effect of confounders on the ppFEV1 decline. RESULTS: The LCI value for predicting ppFEV1 decline >3.7% at the end of one year was 8.2 (area under the curve: 0.80) Multivariable regression analysis showed that the absence of the F508del mutation in at least one allele, LCI >8.2 and initial FEV1 z-score were predictors of a ppFEV1 decline >3.7 (p<0.001). Factors altering ppFEV1 decline>3.7% at the end of one-year evaluated by decision trees were as follows: initial FEV1 z-score, type of CFTR mutation, LCI value and initial weight-for-age z-score. CONCLUSIONS: LCI is sensitive for predicting ppFEV1 decline in patients with ppFEV1 ≥80 along with the initial FEV1-z-score and type of CFTR mutation.

5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function.

Background: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers. Objective: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans. Methods: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts. Results: Pharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil transendothelial migration. In contrast, eosinophil transendothelial migration was not inhibited by siRNA knockdown of HTR1A or HTR1B in eosinophils. Surprisingly, these HTRs were intracellular in endothelial cells and an extracellular supplementation with serotonin did not inhibit eosinophil transendothelial migration. This is consistent with the inability of serotonin to cross membranes, the lack of selective serotonin reuptake receptors on endothelial cells, and the studies showing minimal impact of selective serotonin reuptake inhibitors on asthma. To extend our HTR studies to humans with asthma, we examined the CHIRAH and GALA cohorts for HTR SNPs that affect HTR function or are associated with behavior disorders. A polygenic index of SNPs in HTRs was associated with lower lung function in asthmatics. Conclusions: Serotonin receptors mediate 5HTP inhibition of transendothelial migration and HTR SNPs associate with lower lung function. These results may serve to aid in design of novel interventions for allergic inflammation.

What constitutes an obstructive ventilatory impairment in a pediatric population? A study design.

INTRODUCTION: There is no clear consensus as to what constitutes an obstructive ventilatory impairment (OVI) in pediatric populations. AIM: To determine the percentage of children/adolescents having an OVI among those addressed for spirometry after taking into account the definitions advanced by some international scholarly societies [British Columbia (BC), British thoracic-society (BTS), Canadian thoracic society (CTS), European respiratory society and American thoracic society (ERS-ATS), global initiative for asthma (GINA), Irish college of general practitioners (ICGP), national asthma council (NAC), national institute of clinical excellence (NICE), Société de pneumologie de langue française, Société pédiatrique de pneumologie et allergologie (SPLF-SP2A), and South African thoracic society (SATS)]. METHODS: This bi-centric cross-sectional study involves two medical structures in Sousse/Tunisia, and will encompass children/adolescents aged 6-18 years. A medical questionnaire will be administered, clinical and anthropometric data will be collected, and the spirometric data will be measured by two spirometers. The following six definitions of OVI will be applied: i) GINA: Forced expiratory volume in 1 second (FEV1) < 80% and a FEV1/forced vital capacity (FVC) ≤ 0.90; ii) ICGP: FEV1/FVC < 0.70; iii) ERS-ATS or BTS or SATS or SPLF-SP2A or NAC: FEV1/FVC z-score < -1.645; iv) NICE: FEV1/FVC < 0.70 or FEV1/FVC z-score < -1.645; v) CTS: FEV1/FVC < 0.80 or a FEV1/FVC z-score < -1.645; and vi) ERS: "FEV1 z-score or FEV1/FVC z-score" < -1.645 or "FEV1 or FEV1/FVC" < 0.80. EXPECTED RESULTS: The percentage of children/adolescents having an OVI will significantly vary between the six definitions. CONCLUSION: The frequency of OVI in a pediatric population will depend on the definition chosen.

Assessment of Pulmonary Functions in Parkinson's Disease and Unveiling the Role of Levodopa Therapy: A Cross-Sectional Study.

INTRODUCTION: This investigation aimed to thoroughly characterize the range of pulmonary function abnormalities present in individuals with Parkinson's disease (PD) and to evaluate the effects of levodopa therapy on these respiratory dysfunctions. METHODS:  Ninety-five PD patients diagnosed via the UK Parkinson's Disease Society Brain Bank Diagnostic Criteria were recruited, excluding those with a smoking history or unable to perform pulmonary function tests (PFTs). Severity was assessed using the Hoehn and Yahr Scale. Spirometry-measured PFT parameters (forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow rate (PEFR)) were compared against matched predicted values. The changes in PFT parameters post-levodopa challenge were assessed. RESULTS: Most of the PD patients were aged between 51-60 years, with a mean age of 55.89 ± 8.37 years. Of these, 65.3% were male. A significant proportion of the cohort exhibited restrictive pulmonary patterns (73.7%), while a smaller fraction displayed obstructive (7.4%) or normal (18.9%) pulmonary function patterns. Notably, levodopa treatment correlated with marked improvements in all measured PFT parameters, especially evident in the enhancements from the "off" medication stage to the "on" stage for FVC and FEV1 (P=0.0001). A weak positive correlation between the severity of respiratory restriction and the duration of PD (r = 0.139, P = 0.021) was found, suggesting that PD's progression exerts an increasingly adverse effect on respiratory function over time. CONCLUSION:  The findings of this study illustrate that restrictive pulmonary abnormalities are more prevalent than obstructive patterns in PD patients and that these patients respond favorably to levodopa therapy.

The Effect of Obesity on Severity of Asthma: An Observational Prospective Study from Pakistan.

Objective: The current research study aimed to access the relationship between obesity and asthma exacerbations and severity among adult patients at the outpatient section of a federal hospital (PIMS) in Islamabad, Pakistan. Methods: A cross-sectional research study was carried out on 207 asthma adult patients belonging to different areas and ethnic groups from the country. The study setting was the PIMS hospital, which attracts patients from all over the country due to its facilities and cost-effective treatments. The body mass index (BMI) of asthma patients was calculated using the heights and weights of the study subjects. However, the pulmonary functions were calculated using a computerized spirometer i-e Spirolab III S/N 303681 in line with Winspiro PRO 7.1.version software. It presents the patient's forced vital capacity that expires in the first second of expiration to full (FEV1) in comparison to forced vital capacity (FVC) ratio, that is, Tiffeneau-Pinelli index was also recorded to determine the asthma severity. Results: According to recent surveys, the overall prevalence of patients with overweight and obesity was 29.0% and 23.7%, respectively. A Chi-square test was used, and a statistically significant relationship was observed between BMI and asthma severity (P < 0.001). The adult obese female patients presented poor pulmonary functions. The average FEV1/FVC ratio presented significant variance among four different categories of BMI with P < 0.05. This difference was due to the normal BMI category as the Tiffeneau-Pinelli index, that is, FEV1/FVC in the normal BMI group was significantly lower as compared to that in underweight and obese patients. Conclusion: The study subjects presented raised asthma severity in accordance with the raised BMI. Obese patients presented comparatively raised asthma exacerbations. Moreover, a statistically significant association of gender difference was observed between obesity and asthma severity. It was concluded that adult asthmatic women with obesity presented raised asthma severity as compared to adult asthmatic males.

The relationship of gastroesophageal reflux disease and asthma control.

Purpose: To study whether ACT responses are confounded by gastro-esophageal status (GERD), and if this is in concordance with the variation in Forced Expiratory Volume in 1 second (FEV1%) and Fractional Excretion of Nitric Oxide (FeNO). Materials and Methods: This is a prospective cohort study (n = 307). Patients were surveyed for demographics data, and underwent ACT scoring, FEV1% and FeNO testing. Results: Patients with GERD had mean ACT scores that were 4.1 (p < .001) lower than without-GERD group. Not-well-controlled asthmatics (FEV1% <80, high FeNO) with-GERD had mean ACT scores that were 2.9 (p < .001) for FEV1% <80 and 3.8 (p = .008) for high FeNO lower than without-GERD group respectively. Well-controlled asthmatics (FEV1% ≥80, low FeNO) with-GERD had mean ACT scores that were 5.2 (p < .001) for FEV1% ≥80 and 5.1 (p < .001) for low FeNO lower than without-GERD group respectively. Conclusion: Our study demonstrates that symptoms of GERD can lead to an inaccurate perception of asthma control and ACT as compared to objective measures, such as FEV1% and FeNO. Hence, this can lead to mismanagement of asthma, especially when objective measures are not conducted along with ACT.

Association Between Lung Function of Children and Their Socioeconomic Conditions: A Systematic Review.

Objective: This study aims to evaluate the association between socioeconomic conditions and the lung function of children below 18 years old. Design: Systematic review. Methods: PRISMA guidelines were followed to browse relevant studies from 2013 to 2023. Data from the included studies were extracted after the Newcastle-Ottawa risk of bias tool was applied. Main Outcome: Forced expiratory volume in the first second (FEV1) liters. Results: 20 papers with 89,619 participants were included. Logistic regression model for FEV1 based on multiple SES indices, suggested a positive association between lower respiratory function and a lower SES, with an interquartile odds ratio (OR) of 1.67 (95% CI 1.03-1.34). Conclusion: Children from a lower socioeconomic status (SES) do exhibit lower lung function and addressing the causes of this can contribute to developing preventive public health strategies. Limitations: Lack of appropriate reference values and varied indicators of socioeconomic status in the studies contributed to significant statistical differences. Prospero Registration Number: CRD 42020197658.

Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma.

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.

Treatment with systemic corticosteroid versus placebo for exacerbations of COPD: A systematic review and meta-analysis.

BACKGROUND: For the treatment of COPD exacerbations, systemic corticosteroids are recommended in addition to short-acting bronchodilators. Although there have been several systemic reviews, many of the included studies were conducted before 2007 and a re-evaluation has not been performed since 2014. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety profile of systemic corticosteroids in patients with COPD during exacerbations. METHODS: We searched relevant randomized control trials (RCTs) and analyzed the treatment failure, relapse, lung function, improvement in PaO2 and PaCO2, dyspnea, quality of life (QOL), length of stay in hospital and adverse events including hyperglycemia and mortality as the outcomes of interest. RESULTS: We identified a total of 12 RCTs (N = 1336). Systemic corticosteroids significantly reduced the treatment failure (odds ratios; OR 0.41, 95% confidence intervals; CI 0.25 to 0.67) and hospital length of stay (mean difference; MD -1.57 days, 95% CI -2.36 to -0.78) and improved FEV1 (MD 0.18 L, 95% CI 0.08 to 0.28) and dyspnea (transitional dyspnea index; MD 1.90, 95% CI 0.26 to 3.54) in COPD exacerbations compared to placebo. However, systemic corticosteroids were associated with a significantly higher incidence of adverse events (OR 1.83, 95% CI 1.25 to 2.69) and hyperglycemia (OR 2.94, 95% CI 1.68 to 5.14). CONCLUSIONS: In patients with moderate and severe COPD and severe obstructive impairment during exacerbations, systemic corticosteroids cause more adverse events, including hyperglycemia, than placebo but significantly reduce the treatment failure and hospital length of stay and improve FEV1 and dyspnea.