Pulmonary Function Parameters Research Articles

P171 Clinical experience with the introduction of a programme with CFTR modulators in a paediatric cystic fibrosis centre in Poland - a preliminary report

In 2022, Poland joined the elite group of countries where CFTR modulators (mCFTR) are reimbursed. The aim of this prospective study was the analysis of selected nutritional and pulmonary function parameters and their impact on patient health-related quality of life in CF children before and 3 months after the introduction of mCFTR therapy.

Pulmonary Function Test and Obstructive Sleep Apnea Hypopnea Syndrome in Obese Adults: A Retrospective Study.

We explore risk factors related to severe obstructive sleep apnea (OSA) in obese patients, including pulmonary ventilation function, diffusion function, and impulse oscillometry (IOS) data. The medical records of 207 obese patients who were prepared to undergo bariatric surgery in a hospital from May 2020 to September 2021 were retrospectively reviewed. Polysomnography (PSG), pulmonary ventilation function, diffusion function, and IOS parameters were collected according to the ethical standards of the institutional research committee (registration number: KYLL-202008-144). Logistic regression analysis was used to analyze the related independent risk factors. There were significantly statistical difference in a number of pulmonary ventilation and diffusion function parameters among the non-OSAHS group, the mild-to-moderate OSA group, and the severe OSA group. However, only airway resistance parameters R5%, R10%, R15%, R20%, R25%, and R35% increased with increasing OSA severity and were positively correlated with apnea hypopnea index (AHI). Age (P = 0.012, 1.104 (1.022, 1.192)), body mass index (P< 0.0001, 1.12 (1.057, 1.187)), gender (P = 0.003, 4.129 (1.625, 10.49)), and R25% (P = 0.007, 1.018 (1.005, 1.031)) were independent risk factors for severe OSA. In patients aged 35 to 60, RV/TLC (P = 0.029, 1.272 (1.025, 1.577)) is an independent risk factor for severe OSA. R25% was an independent risk factor for severe OSA in obese individuals, while RV/TLC was also an independent risk factor in those aged 35 to 60. Pulmonary function tests (PFTs), particularly IOS levels, are recommended to assess severe OSA in obese patients.

Health effects of informal precarious workers in occupational environments with high exposure to pollutants.

The aim is to investigate and describe the health conditions of workers who are employed in precarious work settings in Mexico. Specifically, the study aims to provide insight on the health status of workers who are vulnerable due to the informal nature of their employment. Through the evaluation of three different scenarios of precarious employment (n = 110), including workers in mercury miner (workers A), brick-kilns (workers B), and quarries workers (workers C). The study analyzes clinical parameters to determine the workers' renal health condition and assesses their pulmonary function using spirometry. Multivariate analyses and Spearman correlation are performed to determine the contribution of length of service to workers' health parameters. Workers B have the highest incidence of clinical health alterations, with the highest BMI and prediabetes/diabetes index, albumin creatinine ratio, and eGFR. Moreover, pulmonary function parameters show a decrease in %FEV1/FVC in workers B and C compared to workers A, while workers A demonstrate a more significant decrease in %FEV1. Additionally, a negative correlation is observed between the length of service in precarious work settings and lung parameters (r = -0.538, p < 0.001). In conclusion, this study highlights the need to address the issue of precarious employment in Mexico by improving working conditions, access to healthcare and promoting social protection for workers, which can reduce the number of work-related illnesses and deaths and ensure the safety and health of workers.

Spirometric Analysis of Vitamin C and Its Effect on Lung Functions of Athletes

Commonly used vitamins such as vitamin C is seen by many athletes as nutritional supplement rather than a performance enhancing drug that boost pulmonary function parameters. This research work is aimed at investigating the effect of vitamin C on Spirometric parameters of athletes. 100 participants were used, 50 for each test group (Vitamin C) and water as control group. Spirometry and peak flow measurements were carried out on each participant. The vitamin C administered orally at a dose of 1.50mg/kg body weight and 35ml of water given orally, the body mass index (BMI), age, sex considered. Measurements were taken before and after one hour of administration of drugs. The results show mean PEFR male and female for Ascorbic Acid test group as 535.2±207.79L/Min and 322.76±20.39L/Min respectively. Control group PEFR male and female as 364.8±23.20L/Min and 325.6±20.45L/Min respectively. Control groups PEFR male and female as 450.6±51.45L/Min and 290±34.90L/Min for Vitamin C, 318±16.26L/Min and 275.20±14.77L/Min for water respectively. Vitamin C increases PEFR much more than water, ERV, IC, VC and IVC were increased by Ascorbic Acid while water decreased ERV, IC, VC, and IVC. The vitamin C effect shows a significant (p&lt;0.05) increase in PEFR, indicating a minimal response of smooth muscle to sympathomimetic. The research work supports the performance enhancing role of Vitamin C, more pronounced in males than females. The finding of this study actually shows that vitamin C indeed has beneficial effect on pulmonary function which means enhancement of performance of athletes. The relatively lower values in females in this study correspond with the report that progesterone reduces fatigue and lowers exercise tolerance (Van-Haren et al., 1998), the participants have high reserve expiratory abilities. This might be due to the fact that they are athletes, meaning they always engage in active regular bodily exercises.

A Portable Self‐Powered Turbine Spirometer for Rehabilitation Monitoring on COVID‐19

AbstractCoronavirus disease 2019 (COVID‐19) patients may experience persistent impairment of the lungs after recovery and discharge, which can cause a decline in pulmonary function. Therefore, regular pulmonary function tests are essential for COVID‐19 recovered patients, and portable, home‐based pulmonary function test devices are of great significance during the pandemic. Herein, a portable self‐powered turbine spirometer (PSTS) is designed for respiratory flow measurement and assessment of pulmonary function with high accuracy, humidity resistance, good durability, and low cost. The respiratory airflow can directly drive PSTS to produce a sinusoidal signal with a signal‐to‐noise of 40.64 dB. By utilizing the long short‐term memory (LSTM) model, the flow is successfully predicted, and the “lag‐before‐start” and “spin‐after‐stop” defects of the turbine spirometer are eliminated effectively. For pulmonary function tests, the flow‐volume loop curve can be obtained from PSTS, and pulmonary function parameters such as inspiratory capacity (IC), forced vital capacity (FVC) and forced expiratory volume in the first 1 s (FEV1) can be calculated. The accuracy of IC is over 95%, and others can reach over 97%. A portable smart pulmonary function assessment system is further developed and used to test the pulmonary function of COVID‐19 patients one month after symptom onset, demonstrating potential for assessing rehabilitation trends and long‐term follow‐up of COVID‐19 recovered patients.

Environmental and health impacts of household energy conversion on PAHs and their derivatives in PM2.5 in typical areas of northern China

Heavy use of solid fuels in rural households of northern China emits huge amounts of fine particulate matter (i.e., PM2.5) that pose notable indoor air pollution and severe inhalation health risks. In this study, the environmental and health benefits of clean energy substitution were accessed by monitoring indoor and personal exposure to polycyclic aromatic hydrocarbons (PAHs) and their derivatives, and pulmonary function and biological parameters. After substitutions of traditional lump coal and biomass fuels by clean coal, indoor concentrations of parent PAHs (p-PAHs), alkylated PAHs (a-PAHs), oxygenated PAHs (o-PAHs), and nitro PAHs (n-PAHs) reduced by 71 %, 32 %, 70 %, and 76 %, while personal exposure concentrations decreased by 82 %, 87 %, 93 %, and 86 %, respectively. However, the proportion of low molecular weight PAHs increases, especially for 2-ring a-PAHs and 3-ring n-PAHs. Domestic solid fuel burning induces greater damage to the small airway than the large airway. Pulmonary function parameter reductions in the clean coal group are much less than those in the other two fuel groups. Salivary interleukin-6 (IL-6) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) significantly correlated with PAH species, among which p-PAHs and PAHs derivatives strongly with IL-6 and 8-OHdG, respectively. The correlation between PAHs and biomarkers in urine is insignificant. In addition, the use of clean coal can reduce the cancer risk for the four classes of PAHs by 60 %–97 %, mainly owing to the lower contributions from p-PAHs and o-PAHs. The result of the study provides scientific support for clean energy retrofit and an understanding of health benefits from solid fuel substitutions.

The effect of nintedanib on lung functions and survival in idiopathic pulmonary fibrosis: real-life analysis of the Czech EMPIRE registry

IntroductionThe antifibrotic drug nintedanib is used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the effect of nintedanib on antifibrotic treatment outcome in real-world cohorts of Czech EMPIRE registry.Patients/methodsData of 611 Czech IPF subjects, 430 (70%) treated with nintedanib (NIN group), 181 (30%) with no-antifibrotic treatment (NAF group) were analysed. The influence of nintedanib on overall survival (OS), pulmonary function parameters as forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO), as well as GAP score (gender, age, physiology) and and CPI (composite physiological index) were investigated.ResultsDuring 2 year follow-up we observed that nintedanib treated patients had longer OS, compared to those treated with no-antifibrotic drugs (p < 0.00001). Nintedanib reduces risk of mortality over no-antifibrotic treatment by 55% (p < 0.001). We have observed no significant difference in the rate of FVC and DLCO decline between the NIN and NAF group. Changes within 24 months from baseline in CPI were not significant between the groups (NAF and NIN).ConclusionOur real-practice study showed the benefit of nintedanib treatment on survival. There were no significant differences between NIN and NAF groups in changes from baseline in FVC %, DLCO % predicted and CPI.

Fluid balance in critically ill children with lower respiratory tract viral infection: a cohort study

BackgroundIncreasing evidence has associated positive fluid balance of critically ill patients with poor outcomes. The aim of this study was to explore the pattern of daily fluid balances and their association with outcomes in critically ill children with lower respiratory tract viral infection.MethodsA retrospective single-center study was conducted, in children supported with high-flow nasal cannula, non-invasive ventilation, or invasive ventilation. Median (interquartile range) daily fluid balances, cumulative fluid overload (FO) and peak FO variation, indexed as the % of admission body weight, over the first week of Pediatric Intensive Care Unit admission, and their association with the duration of respiratory support were assessed.ResultsOverall, 94 patients with a median age of 6.9 (1.9–18) months, and a respiratory support duration of 4 (2–7) days, showed a median (interquartile range) daily fluid balance of 18 (4.5–19.5) ml/kg at day 1, which decreased up to day 3 to 5.9 (− 14 to 24.9) ml/kg and increased to 13 (− 11 to 29.9) ml/kg at day 7 (p = 0.001). Median cumulative FO% was 4.6 (− 0.8 to 11) and peak FO% was 5.7 (1.9–12.4). Daily fluid balances, once patients were stratified according to the respiratory support, were significantly lower in those requiring mechanical ventilation (p = 0.003). No correlation was found between all examined fluid balances and respiratory support duration or oxygen saturation, even after subgroup analysis of patients with invasive mechanical ventilation, or respiratory comorbidities, or bacterial coinfection, or of patients under 1 year old.ConclusionsIn a cohort of children with bronchiolitis, fluid balance was not associated with duration of respiratory support or other parameters of pulmonary function.

Long-Term Radiographic and Pulmonary Function Outcomes After Dual Growing-Rod Treatment for Severe Early-Onset Scoliosis.

We evaluated long-term outcomes (radiographic parameters and pulmonary function) at a minimum follow-up of 5 years after use of dual growing rods (DGRs) to treat severe early-onset scoliosis (sEOS). Among a total of 112 patients who were diagnosed with early-onset scoliosis (EOS) and were treated with DGRs between 2006 and 2015, 52 patients had sEOS, with a major Cobb angle of >80°. Of these patients, 39 with a minimum follow-up of 5 years had complete radiographic and pulmonary function test results and were included. The Cobb angle of the major curve, T1-S1 height, T1-T12 height, and maximum kyphosis angle in the sagittal plane were measured on radiographs. Pulmonary function test results were collected in all patients before the initial operation (preoperatively), 12 months after the initial operation (postoperatively), and at the last follow-up. The changes in pulmonary function and complications during treatment were analyzed. The mean age of patients before the initial operation was 7.7 ± 1.2 years, and the mean follow-up period was 75.0 ± 14.1 months. The mean number of lengthenings was 4.5 ± 1.3, and the mean interval between lengthenings was 11.2 ± 2.1 months. The Cobb angle improved from 104.5° ± 18.2° preoperatively to 38.1° ± 10.1° after the initial surgical procedure (postoperatively) and 21.9° ± 8.6° at the final follow-up. The T1-S1 height increased from 25.1 ± 4.0 cm preoperatively to 32.4 ± 3.5 cm postoperatively and to 39.5 ± 4.0 cm at the final follow-up. However, no significant difference was detected between the increased pulmonary function parameters at 1 year and those before the operation (p > 0.05), except for residual volume, whereas pulmonary function parameters had significantly increased at the final follow-up (p < 0.05). During the treatment period, 17 complications occurred in 12 patients. DGRs are effective in treating sEOS in the long term. They allow longitudinal growth of the spine, and the correction of the spinal deformity can provide conditions that make improving pulmonary function possible in patients with sEOS. Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Identification and validation of chemokine system-related genes in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with limited therapeutic options. Recent studies have demonstrated that chemokines play a vital role in IPF pathogenesis. In the present study, we explored whether the gene signature associated with chemokines could be used as a reliable biological marker for patients with IPF. Chemokine-related differentially expressed genes (CR-DEGs) in IPF and control lung tissue samples were identified using data from the Gene Expression Omnibus database. A chemokine-related signature of the diagnostic model was established using the LASSO-Cox regression. In addition, unsupervised cluster analysis was conducted using consensus-clustering algorithms. The CIBERSORT algorithm was used to calculate immune cell infiltration across patient subgroups. Finally, we established a mouse model of bleomycin-induced pulmonary fibrosis and a model of fibroblasts treated with TGFβ1. Expression levels of chemokine-related signature genes were determined using real-time quantitative polymerase chain reaction (RT-qPCR). We established a chemokine-related eleven-gene signature of a diagnostic model consisting of CXCL2, CCRL2, ARRB1, XCL1, GRK5, PPBP, CCL19, CCL13, CCL11, CXCL6, and CXCL13, which could easily distinguish between IPF patients and controls. Additionally, we identified two subtypes of IPF samples based on chemokine-related gene expression. Pulmonary function parameters and stromal scores were significantly higher in subtype 1 than in subtype 2. Several immune cell types, especially plasma cells and macrophages, differ significantly between the two subtypes. RT-qPCR results showed that the expression levels of Cxcl2 and Ccl2 increased considerably in bleomycin-induced mice. Meanwhile, Arrb1, Ccrl2, Grk5, and Ppbp expression was significantly reduced. Furthermore, multiple chemokine-related genes were altered in TGFβ1 or TNFα-induced fibroblast cells. A novel chemokine-related eleven-signature of diagnostic model was developed. These genes are potential biomarkers of IPF and may play essential roles in its pathogenesis.

Biomarkers of cellular senescence in idiopathic pulmonary fibrosis

BackgroundCellular senescence is a cell fate in response to diverse forms of age-related damage and stress that has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The associations between circulating levels of candidate senescence biomarkers and disease outcomes have not been specifically studied in IPF. In this study we assessed the circulating levels of candidate senescence biomarkers in individuals affected by IPF and controls and evaluated their ability to predict disease outcomes.MethodsWe measured the plasma concentrations of 32 proteins associated with senescence in Lung Tissue Research Consortium participants and studied their relationship with the diagnosis of IPF, parameters of pulmonary and physical function, health-related quality of life, mortality, and lung tissue expression of P16, a prototypical marker of cellular senescence. A machine learning approach was used to evaluate the ability of combinatorial biomarker signatures to predict disease outcomes.ResultsThe circulating levels of several senescence biomarkers were significantly elevated in persons affected by IPF compared to controls. A subset of biomarkers accurately classified participants as having or not having the disease and was significantly correlated with measures of pulmonary function, health-related quality of life and, to an extent, physical function. An exploratory analysis revealed senescence biomarkers were also associated with mortality in IPF participants. Finally, the plasma concentrations of several biomarkers were associated with their expression levels in lung tissue as well as the expression of P16.ConclusionsOur results suggest that circulating levels of candidate senescence biomarkers are informative of disease status, pulmonary and physical function, and health-related quality of life. Additional studies are needed to validate the combinatorial biomarkers signatures that emerged using a machine learning approach.

Abstract 1991: Remodeling the microenvironment of osteosarcoma lung metastases with inhaled CSF-1Ri immunotherapy

Abstract Osteosarcoma (OS) metastasizes primarily and almost exclusively to the lungs. The survival rate decreases significantly for patients who develop OS lung metastasis (OSLM). Purpose: To assess the safety and efficacy of colony-stimulating factor-1 receptor inhibitor (CSF-1Ri) (Pexidartinib; PLX) in shifting the OSLM tumor microenvironment (TME) to an anti-tumorigenic state upon local delivery to lungs of a syngeneic mouse model of OSLM. Methods: The safety of PLX upon repeated pulmonary administration (9 doses, every other day at 2 mg/kg) in healthy BALB/c mice was assessed using health scoring, pulmonary mechanics, molecular and cellular composition of bronchoalveolar lavage fluid (BALF), blood count and plasma biochemistry, and H&amp;E of lungs and liver. To establish the OSLM model, murine OS cells, expressing bioluminescent and fluorescent genes (K7M2-Luc-tdT), were used. Mice bearing OSLM were randomized into two groups (vehicle and PLX) and treated over 3 weeks. Tumor burden was evaluated using bioluminescent imaging (BLI) and lung weight. The treatment impact on the abundance and phenotype of tumor-associated macrophages (TAMs) and their CSF-1R expression as well as on the abundance of tumor-infiltrating lymphocytes and their expression to PD-1 were investigated using immunofluorescence, flow cytometry, and western blot. Results: PLX is well tolerated upon local lung administration with all safety markers indicating no alteration compared to naïve and vehicle controls. Treatment did not affect health scores. We did not detect any functional or mechanical alteration on the lungs or systemically (including liver); no marked differences in pulmonary function parameters, proinflammatory cytokines, nor infiltrating differential cell count obtained from BALF were observed. Both total blood count and liver enzymes were within normal range. As a measure of efficacy, treatment with PLX via local lung administration reduced tumor burden, indicated by the in vivo BLI and lung weight. Notably, PLX significantly decreased the abundance of total TAMs, with a more pronounced effect on pro-tumorigenic alternatively-activated (M2-like) TAMs phenotype, thus leading to a 22-fold increase in M1/M2 ratio. PLX further led to a marked decrease in tumor-promoting T regulatory cells (Treg), increase in the CD8/Treg ratio, and decrease in PD-1+ percentage in CD8 T cells in the TME, indicating a shift to a more immunogenic tumor phenotype. Conclusions: We demonstrated that repeated doses of PLX is safe upon local delivery to the lungs of murine model of OSLM, with no alternations in lungs or liver tissue. We further showed that PLX reduces tumor burden, which correlates with a change in the immune phenotype of the OSLM toward a more anti-tumorigenic profile. These results are clinically relevant as PLX has been approved by the FDA, thus opening opportunities for its repurposing to support standard of care therapy in OSLM. Citation Format: Fatemah S. Sunbul, Sulaiman S. Alhudaithi, Rashed M. Almuqbil, Hanming Zhang, Raneem R. Aldaqqa, Shane Albin, Rebecca L. Heise, Valentina Robila, Matthew S. Halquist, Sarah W. Gordon, Paula D. Bos, Sandro R. da Rocha. Remodeling the microenvironment of osteosarcoma lung metastases with inhaled CSF-1Ri immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1991.

Investigating the Effect of Welding Fume in Pulmonary Function of Welders in an Automobile Industry.

Respiratory exposure to welding fumes directly or indirectly, in the long run, can lead to systematic effects among welders. This study aimed to investigate respiratory symptoms and pulmonary function parameters among welders working in the automotive industry. This cross-sectional study was performed among 2304 workers from two groups in the manufacturing and administrative staff (as exposure and control groups). Pulmonary function parameters and respiratory symptoms were collected through periodic spirometry examinations and a standard respiratory symptoms questionnaire. Exposure to welding fumes was obtained from the annual measurement data based on the NIOSH7300 method. Data were analyzed using SPSS software version 22 and linear and multiple regression statistical tests. The mean age of the subjects in the case and control groups were 37.5 and 38.5 years, respectively. All the apparent symptoms of respiratory diseases (cough, sputum) in the welder's group were more than in the control group. Also, there was a significant difference between the respiratory symptoms in the two groups (P < 0.001). The mean value of all spirometric parameters (FVC, FEV1, FEV1/FVC, FEF25-75, PEF) in the case group (welders) was significantly lower than the control group. The results of this study revealed that the variables of age and work experience effectively reduce all spirometric parameters of welders. Also, regarding the effect of metal vapors, a significant relationship has been seen between Cu in welding fume and FEF25-75 and FEV1 spirometric parameters.

The Internal COVID-19 Database Registry: A Rural, Community Hospital’s Experience with the Pandemic

Background: The COVID-19 pandemic has brought to light several long-term complications that may be challenging for clinicians to manage. Therefore, it is imperative for physicians to be able to identify patients at risk for infection and to understand the deleterious physiologic and clinical effects the virus can have on long-term lung function. Methods: The authors utilized the internal COVID-19 database registry at a rural, community hospital to identify the presence of pulmonary-specific conditions that may have predisposed the patient population to infection. Data were collected from 1,329 patients admitted to the hospital between March 2020 and November 2021. Data regarding patient demographics, vaccination status, baseline pulmonary conditions, and pulmonary function tests were collected. All statistical analysis was carried out in R statistical programming language (R Core Team, 2021). Results: The pulmonary condition that had the highest mortality rate (42.86%) was obesity hypoventilation syndrome; however, the total number of patients with this diagnosis was only 7. With regards to change in pulmonary function parameters following admission, the only variable that was found to be statistically significant was a decrease in DLCO (diffusing capacity) for patients who survived. Interestingly, there was no statistically significant difference in mortality among vaccinated patients. Conclusions: Although some confounding variables may exist, the registry database may prove clinically useful to help guide physicians in establishing disease patterns and better managing long-term complications from COVID-19. Additional variables of interest to measure may include new imaging findings of pulmonary fibrosis, development of pulmonary hypertension, and new oxygen requirements.

Lung function measurements in preclinical research: What has been done and where is it headed?

Due to the close interaction of lung morphology and functions, repeatable measurements of pulmonary function during longitudinal studies on lung pathophysiology and treatment efficacy have been a great area of interest for lung researchers. Spirometry, as a simple and quick procedure that depends on the maximal inspiration of the patient, is the most common lung function test in clinics that measures lung volumes against time. Similarly, in the preclinical area, plethysmography techniques offer lung functional parameters related to lung volumes. In the past few decades, many innovative techniques have been introduced for in vivo lung function measurements, while each one of these techniques has their own advantages and disadvantages. Before each experiment, depending on the sensitivity of the required pulmonary functional parameters, it should be decided whether an invasive or non-invasive approach is desired. On one hand, invasive techniques offer sensitive and specific readouts related to lung mechanics in anesthetized and tracheotomized animals at endpoints. On the other hand, non-invasive techniques allow repeatable lung function measurements in conscious, free-breathing animals with readouts related to the lung volumes. The biggest disadvantage of these standard techniques for lung function measurements is considering the lung as a single unit and providing only global readouts. However, recent advances in lung imaging modalities such as x-ray computed tomography and magnetic resonance imaging opened new doors toward obtaining both anatomical and functional information from the same scan session, without the requirement for any extra pulmonary functional measurements, in more regional and non-invasive manners. Consequently, a new field of study called pulmonary functional imaging was born which focuses on introducing new techniques for regional quantification of lung function non-invasively using imaging-based techniques. This narrative review provides first an overview of both invasive and non-invasive conventional methods for lung function measurements, mostly focused on small animals for preclinical research, including discussions about their advantages and disadvantages. Then, we focus on those newly developed, non-invasive, imaging-based techniques that can provide either global or regional lung functional readouts at multiple time-points.

Monitoring small airway dysfunction in connective tissue disease-related interstitial lung disease: a retrospective and prospective study

BackgroundSmall airway dysfunction (SAD), a hallmark of early lung function abnormality, is a major component of several chronic respiratory disorders. The role of SAD in patients with connective tissue disease-related interstitial lung disease (CTD-ILD) has not been explored.MethodsWe conducted a two-parts (retrospective and prospective) study to collect pulmonary function tests from CTD-ILD patients. SAD was defined as at least two of the three measures (MMEF, FEF 50%, and FEF 75%) must be 65% of predicted values. Spearman correlation coefficient was used to evaluate association between SAD and other pulmonary function parameters. Mixed effects regression modeling analysis was used to assess response to treatment.ResultsCTD-ILD patients with SAD and without SAD were compared in this study. In the retrospective study, pulmonary function tests (PFTs) from 491 CTD-ILD patients were evaluated, SAD were identified in 233 (47.5%). CTD-ILD patients with SAD were less smokers (17.6% vs. 27.9%, p = 0.007) and more females (74.3% vs. 64.0%, p = 0.015) than those without SAD. CTD-ILD patients with SAD had lower vital capacity (% predicted FVC, 70.4 ± 18.3 vs. 80.0 ± 20.9, p < 0.001) and lower diffusion capacity (% predicted DLCO, 58.8 ± 19.7 vs. 63.8 ± 22.1, p = 0.011) than those without SAD. Among 87 CTD-ILD patients prospectively enrolled, significant improvement in % predicted FVC was observed at 12-months follow-up (6.37 ± 1.53, p < 0.001 in patients with SAD; 5.13 ± 1.53, p = 0.002 in patients without SAD), but not in diffusion capacity and SAD parameters.ConclusionIn our cohort, about half of CTD-ILD patients have SAD, which is less frequent in smokers and more common in female patients. CTD-ILD patients with SAD have worse pulmonary function compared to those without SAD. Improvement of FVC but no improvement of SAD was observed in CTD-ILD patients after treatment.

Cesium exposure and pulmonary function decline: Potential mediating role of oxidative stress in chronic obstructive pulmonary disease patients

Cesium (Cs) is one of alkali metals. Persistent low-dose Cs exposure damages pulmonary function in the general population. However, the associations between Cs exposure and pulmonary function alternation are inconsistent in chronic obstructive pulmonary disease (COPD) patients. Thus, the goal of this study was to estimate the association between blood Cs concentration and pulmonary function alternation and the potential role of oxidative stress in this association. Serum 8-iso-prostaglandin F2α (8-iso-PGF2α) and blood Cs were measured. A generalized additive model and smoothed curve fitting found a non-linear relationship between blood Cs concentration and pulmonary function in COPD patients. Under the inflection point of blood Cs, per 1-unit increase of blood Cs was related with reductions of 0.592 L (95% CI: −1.181, −0.004) in FVC and 32.479% (95% CI: −55.278, −9.680) in predicted FEV1% with adjustment for confounding variables. Smoking status aggravated Cs-caused pulmonary function reduction in COPD patients. Sensitivity analyses hinted that our results remained robust. Moreover, a negatively linear correlation (β = 0.232; 95% CI: 0.105, 0.359) between blood Cs within a certain range and serum 8-iso-PGF2α was observed. Further investigation elucidated serum 8-iso-PGF2α was inversely correlated with pulmonary function parameters in COPD patients. Additionally, mediation analysis suggested that 8-iso-PGF2α mediated 6.70% and 8.36% of the associations between blood Cs with the reductions of FEV1 and predicted FEV1%, respectively. Consequently, blood Cs was inversely associated with pulmonary function parameters, but positively related with serum 8-iso-PGF2α. Oxidative stress may exert an important role in mediating Cs exposure-associated pulmonary function reduction in COPD patients.

Diaphragmatic ultrasonography in patients with IPF: Is diaphragmatic structure and mobility related to fibrosis severity and pulmonary functional changes?

There is evidence to suggest that dyspnea and impaired exercise capacity are associated with respiratory muscle dysfunction in idiopathic pulmonary fibrosis (IPF) patients. We aimed to evaluate the functions of the diaphragm with ultrasonography (US) and to determine the correlation of the data obtained with the pulmonary function parameters of the patients, exercise capacity, and the extent of fibrosis radiologically. Diaphragmatic mobility, thickness, and thickening fraction (TF) were measured by ultrasonography in IPF patients and the control group. The correlation between these measurements, pulmonary function tests (PFT), six-minute walking test (6MWT), mMRC score, and total fibrosis score (TFS) was evaluated. Forty-one IPF patients and twenty-one healthy volunteers were included in the study. No difference was found between the patient and control groups in diaphragmatic mobility during quiet breathing (QB) on ultrasound (2.35 cm and 2.56 cm; p= 0.29). Diaphragmatic mobility during deep breathing (DB) was found to be lower in the patient group when compared to the control group (5.02 cm and 7.66 cm; p<0.0001). Diaphragmatic thickness was found to be higher during QB and DB in IPF patients (0.33 cm and 0.31 cm, p= 0.043; 0.24 cm and 0.22 cm, p= 0.045). No difference was found between the two groups in terms of thickening fraction (39.37%, 44.16%; p= 0.49). No significant correlation was found between US measurements and PFT, 6MWT, mMRC score, and TFS in IPF patients (p> 0.05). The functions of the diaphragm do not appear to be affected in patients with mild-to-moderate restrictive IPF. This study showed that there was no relationship between diaphragmatic functions and respiratory function parameters and the extent of fibrosis. Further studies, including advanced stages of the disease, are needed to understand the changes in diaphragmatic functions in IPF and to determine whether this change is associated with respiratory function parameters and the extent of fibrosis.

Hypochromic red cells as a prognostic indicator of survival among patients with systemic sclerosis screened for pulmonary hypertension

BackgroundPatients with systemic sclerosis (SSc) are frequently affected by iron deficiency, particularly those with pulmonary hypertension (PH). The first data indicate the prognostic importance of hypochromic red cells (% HRC) > 2% among patients with PH. Hence, the objective of our study was to investigate the prognostic value of % HRC in SSc patients screened for PH.MethodsIn this retrospective, single-center cohort study, SSc patients with a screening for PH were enrolled. Clinical characteristics and laboratory and pulmonary functional parameters associated with the prognosis of SSc were analyzed using uni- and multivariable analysis.ResultsFrom 280 SSc patients screened, 171 could be included in the analysis having available data of iron metabolism (81% female, 60 ± 13 years of age, 77% limited cutaneous SSc, 65 manifest PH, and 73 pulmonary fibrosis). The patients were followed for 2.4 ± 1.8 (median 2.4) years. HRC > 2% at baseline was significantly associated with worse survival in the uni- (p = 0.018) and multivariable (p = 0.031) analysis independent from the presence of PH or pulmonary parenchymal manifestations. The combination of HRC > 2% and low diffusion capacity for carbon monoxide (DLCO) ≤ 65% predicted was significantly associated with survival (p < 0.0001).ConclusionThis is the first study reporting that HRC > 2% is an independent prognostic predictor of mortality and can possibly be used as a biomarker among SSc patients. The combination of HRC > 2% and DLCO ≤ 65% predicted could serve in the risk stratification of SSc patients. Larger studies are required to confirm these findings.

A Causal Atlas on Comorbidities in Idiopathic Pulmonary Fibrosis: A Bidirectional Mendelian Randomization Study

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with a high burden of both pulmonary and extrapulmonary comorbidities. Do these comorbidities have causal relationships with IPF? We searched PubMed to pinpoint possible IPF-related comorbid conditions. Bidirectional Mendelian randomization (MR) was performed using summary statistics from the largest genome-wide association studies for these diseases to date in a two-sample setting. Findings were verified using multiple MR approaches under different model assumptions, replication datasets for IPF, and secondary phenotypes. A total of 22 comorbidities with genetic data available were included. Bidirectional MR analyses showed convincing evidence for two comorbidities and suggestive evidence for four comorbidities. Gastroesophageal reflux disease, VTE, and hypothyroidism were associated causally with an increased risk of IPF, whereas COPD was associated causally with a decreased risk of IPF. For the reverse direction, IPF showed causal associations with a higher risk of lung cancer, but a reduced risk of hypertension. Follow-up analyses of pulmonary function parameters and BP measures supported the causal effect of COPD on IPF and the causal effect of IPF on hypertension. The present study suggested the causal associations between IPF and certain comorbidities from a genetic perspective. Further research is needed to understand the mechanisms of these associations.