Lung Function In People Research Articles

Therapeutic Drug Monitoring of Elexacaftor, Tezacaftor, and Ivacaftor in Adult People with Cystic Fibrosis.

Elexacaftor, tezacaftor, and ivacaftor (ETI) have significantly improved lung function in people with cystic fibrosis (pwCF). Despite exceptional improvements in most cases, treatment-related inter-subject variability and drug-drug interactions that complicate modulator therapy have been reported. This retrospective analysis presents data on the serum concentration of ETI in our pwCF with full or reduced dosage from August 2021 to December 2023 via routine therapeutic drug monitoring (TDM). The data were compared with the maximum drug concentrations (Cmax) from the pharmaceutical company's summary of product characteristics. A total of 786 blood samples from 155 pwCF (41% female, 59% male) were analyzed. The examinations were divided into four groups: full dose within the given tmax (38.5% of all measurements), full dose outside the tmax (29%), reduced dose within the tmax (19.2%), and reduced dose outside the tmax (13.2%). In pwCF receiving the full dose and blood taken within the tmax, 45.3% of serum concentrations of elexacaftor, 51.1% of serum concentrations of ivacaftor, and 8.9% of serum concentrations of tezacaftor were found to be above the Cmax, respectively. For those on reduced doses within the tmax, 24.5% had a serum concentration of elexacaftor, 23.2% had a serum concentration of ivacaftor, and 2.5% had a serum concentration of tezacaftor above the Cmax, respectively. Many pwCF under ETI therapy have Cmax values for elexacaftor and ivacaftor above the recommended range, even on reduced doses or before the tmax was reached. This highlights the value of a TDM program. Further pharmacokinetic studies are necessary.

Lung function decline in people with serious mental illness: A call to action

This prospective observational study aimed to evaluate the rate of change in forced expiratory volume in the first second (FEV1) and to explore the factors associated with changes in FEV1 in people with serious mental illness (SMI). Sixty subjects diagnosed with schizophrenia or bipolar disorder who were smokers and without history of respiratory illness agreed to participate. The mean (range) follow-up period was 3.54 (3.00–4.98) years. The mean (standard deviation) annual rate of change in FEV1 decreased by 39.1 (105.2) mL/year. Thirty-one (51.7 %) patients experienced a decrease in the FEV1 ≥40 mL/year (i.e. a rapid decline). The factors associated with the absolute change in FEV1 were the baseline International Physical Activity Questionnaire activity score in metabolic equivalents of tasks (β 0.145, 95 % confidence interval [CI] 0.043 to 0.246; p = 0.005), baseline FEV1 (β -0.025, 95 % CI -0.076 to 0.027; p = 0.352), and the interaction term of both variables (β -3.172e-05, 95 % CI -6.025e-05 to -0.319e-05; p = 0.029). The factors associated with rapid FEV1 decline were income (odds ratio [OR] 0.999, 95 % CI 0.995 to 1.003; p = 0.572), the rate of change in abdominal circumference (OR 0.000, 95 % CI 0.000 to 0.890; p = 0.081), and the interaction term of both variables (OR 1.038, 95 % CI 1.010 to 1.082; p = 0.026). In conclusion, a substantial proportion of people with SMI experienced a rapid decrease in FEV1. If our results are confirmed in larger samples, the routine evaluation of lung function in people with SMI would be an opportunity to identify individuals at greater risk of morbidity and mortality.

A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis.

Ivacaftor (IVA) has been shown to change the trajectory of cystic fibrosis (CF) disease progression by slowing the rate of lung function decline in clinical studies. Long-term real-world data help to confirm the durability of this response. This non-interventional, longitudinal study used data from the US CF Foundation Patient Registry to describe the annualized rate of change in lung function in people with CF receiving IVA. The IVA-treated cohort included people with CF aged ≥ 6years who had ≥ 1 CF transmembrane conductance regulator (CFTR)-gating mutation and initiated IVA between 31 January 2012 and 31 December 2018. An age-matched comparator cohort included people with CF heterozygous for the F508del-CFTR mutation and a minimal function mutation (R117H excluded) and had not received CFTR modulator therapy. Baseline characteristics were balanced using standardized mortality ratio (SMR) weights computed from estimated propensity scores. The annualized rate of change in percent predicted forced expiratory volume in 1s (ppFEV1) was estimated over 5years and used to calculate the relative annualized rate of change in lung function in the IVA-treated versus comparator cohorts. In the 5-year follow-up period, 548 people were in the IVA-treated and 541 in the comparator cohorts after SMR weighting. The annualized rate of change in ppFEV1 over 5years was -1.23 (95% CI -1.45, -1.03) and -2.03 (-2.16, -1.90) percentage points in the IVA-treated and comparator cohorts, respectively. There was a 39% reduction (95% CI: 28, 50) in the rate of lung function decline in the IVA-treated versus comparator cohort over 5years. Findings were generally consistent with those of shorter follow-up periods. IVA showed a durable clinical benefit by slowing the rate of lung function decline over 5years. Results support a sustained and consistent impact of IVA on lung function trajectory in people with CF. Word count: 300 (limit: 300 words).

Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells

BackgroundCystic Fibrosis causing mutations in the gene CFTR, reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations. A pilot trial of Ivacaftor supported its potential efficacy for the treatment of mucus obstruction in COPD. These findings prompted the search for CFTR potentiators that are more effective in ameliorating cigarette-smoke (CS) induced mucostasis.MethodsSmall molecule potentiators, previously identified in CFTR binding studies, were tested for activity in augmenting CFTR channel activity using patch clamp electrophysiology in HEK-293 cells, a fluorescence-based assay of membrane potential in Calu-3 cells and in Ussing chamber studies of primary bronchial epithelial cultures. Addition of cigarette smoke extract (CSE) to the solutions bathing the apical surface of Calu-3 cells and primary bronchial airway cultures was used to model COPD. Confocal studies of the velocity of fluorescent microsphere movement on the apical surface of CSE exposed airway epithelial cultures, were used to assess the effect of potentiators on CFTR-mediated mucociliary movement.ResultsWe showed that SK-POT1, like VX-770, was effective in augmenting the cyclic AMP-dependent channel activity of CFTR. SK-POT-1 enhanced CFTR channel activity in airway epithelial cells previously exposed to CSE and ameliorated mucostasis on the surface of primary airway cultures.ConclusionTogether, this evidence supports the further development of SK-POT1 as an intervention in the treatment of COPD.

P. aeruginosa tRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in cystic fibrosis.

Although tobramycin increases lung function in people with cystic fibrosis (pwCF), the density of Pseudomonas aeruginosa (P. aeruginosa) in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is not completely understood. Here, we demonstrate that tobramycin increases 5' tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by laboratory and CF clinical isolates of P. aeruginosa. The 5' tRNA-fMet halves are transferred from OMVs into primary CF human bronchial epithelial cells (CF-HBEC), decreasing OMV-induced IL-8 and IP-10 secretion. In mouse lungs, increased expression of the 5' tRNA-fMet halves in OMVs attenuated KC (murine homolog of IL-8) secretion and neutrophil recruitment. Furthermore, there was less IL-8 and neutrophils in bronchoalveolar lavage fluid isolated from pwCF during the period of exposure to tobramycin versus the period off tobramycin. In conclusion, we have shown in mice and in vitro studies on CF-HBEC that tobramycin reduces inflammation by increasing 5' tRNA-fMet halves in OMVs that are delivered to CF-HBEC and reduce IL-8 and neutrophilic airway inflammation. This effect is predicted to improve lung function in pwCF receiving tobramycin for P. aeruginosa infection.NEW & NOTEWORTHY The experiments in this report identify a novel mechanism, whereby tobramycin reduces inflammation in two models of CF. Tobramycin increased the secretion of tRNA-fMet halves in OMVs secreted by P. aeruginosa, which reduced the OMV-LPS-induced inflammatory response in primary cultures of CF-HBEC and in mouse lung, an effect predicted to reduce lung damage in pwCF.

Study design of BI 1015550 for idiopathic pulmonary fibrosis and progressive pulmonary fibrosis: a plain language summary

What is this summary about? Two ongoing clinical studies are part of a programme called FIBRONEER. The FIBRONEER studies are testing the drug BI 1015550 as a treatment for people with idiopathic pulmonary fibrosis (IPF) and people with progressive pulmonary fibrosis (PPF). IPF is a severe lung disease where scar tissue builds up in the lungs. The ‘idiopathic’ part means that doctors do not know the cause of the lung scarring. PPF is a general term to describe the worsening of lung scarring in any disease where scar tissue forms in the lungs, both from known causes such as other underlying diseases and for unknown reasons. While IPF can be considered to be a typical form of worsening lung scarring, in clinical studies, IPF and PPF are usually considered separately. In both IPF and PPF, scar tissue builds up in the lungs, making them smaller and no longer able to take in oxygen well. This leads to difficulty in breathing and getting oxygen to the tissues, making it difficult to perform daily activities and reducing the patient's quality of life. The symptoms and outcomes of PPF are often similar to IPF. What study drug is being investigated? BI 1015550 is a new study drug being developed to reduce scarring in the lungs in IPF and PPF. In the FIBRONEER studies, some participants are taking BI 1015550 and others are taking placebo. The placebo looks identical to BI 1015550 but does not contain any medicine. Researchers will compare the study drug to placebo to find out how well the study drug works. Participants may also take another approved medicine to treat their lung scarring. The FIBRONEER studies are investigating the effects of BI 1015550 alone and in combination with any existing medicines the participants are taking. The goal is to see whether BI 1015550 can slow down or stop a decline in lung function in people with IPF and PPF, and how well it is tolerated.

Use of elexacaftor/tezacaftor/ivacaftor leads to changes in detection frequencies of Staphylococcus aureus and Pseudomonas aeruginosa dependent on age and lung function in people with cystic fibrosis

ObjectivesThe impressive improvements of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) function by elexacaftor/tezacaftor/ivacaftor (ETI) result in changes in the detection frequencies of Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). We assessed determinants of the response to ETI with regards to SA and PA detection frequencies as documented in the German CF registry for people with CF (pwCF) ≥12 years. MethodsWe evaluated changes in the detection frequencies of SA and PA for 21 months before and after initiation of ETI and used different statistical tests to identify determinants of detection changes. ResultsWe included data from 1092 pwCF with results from culture-dependent diagnostics for SA and PA detection from 7944 microbiological samples before and 6.845 microbiological samples after initiation of ETI. Detections of SA decreased from 54.3% to 44.3% and 40.2% and those of PA from 39.9% to 31.9% and 22.6% 3 and 21 months after initiation of therapy, respectively (all P <0.001). Reduction of SA and PA were observed in throat swabs and sputa, associated significantly with age, previous lung function, and were dependent on pre-ETI colonization status. ConclusionsThe different patterns of reductions of SA and PA suggest that pathogen-specific biological processes govern the responsiveness of microbiological colonization towards ETI in pwCF.

Long-term exposure to low concentrations of air pollution and decline in lung function in people with idiopathic pulmonary fibrosis: Evidence from Australia.

Little is known about the association between ambient air pollution and idiopathic pulmonary fibrosis (IPF) in areas with lower levels of exposure. We aimed to investigate the impact of air pollution on lung function and rapid progression of IPF in Australia. Participants were recruited from the Australian IPF Registry (n = 570). The impact of air pollution on changes in lung function was assessed using linear mixed models and Cox regression was used to investigate the association with rapid progression. Median (25th-75th percentiles) annual fine particulate matter (<2.5 μm, PM2.5 ) and nitrogen dioxide (NO2 ) were 6.8 (5.7, 7.9) μg/m3 and 6.7 (4.9, 8.2) ppb, respectively. Compared to living more than 100 m from a major road, living within 100 m was associated with a 1.3% predicted/year (95% confidence interval [CI] -2.4 to -0.3) faster annual decline in diffusing capacity of the lungs for carbon monoxide (DLco). Each interquartile range (IQR) of 2.2 μg/m3 increase in PM2.5 was associated with a 0.9% predicted/year (95% CI -1.6 to -0.3) faster annual decline in DLco, while there was no association observed with NO2 . There was also no association between air pollution and rapid progression of IPF. Living near a major road and increased PM2.5 were both associated with an increased rate of annual decline in DLco. This study adds to the evidence supporting the negative effects of air pollution on lung function decline in people with IPF living at low-level concentrations of exposure.

Impaired lung function in multiple sclerosis: a single-center observational study in 371 persons.

Abnormal lung function in people with multiple sclerosis (PwMS) could be considered as the result of muscle weakness or MS-specific structural central nervous system (CNS) abnormalities as a precipitant factor for the worsening of motor impairment or cognitive symptoms. This is across-sectional observational study in PwMS. Forced spirometry was conducted, and normative metrics of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the relation FEV1/FVC were calculated. Qualitative and quantitative brain magnetic resonance imaging (MRI) examinations were carried out. A total of 371 PwMS were included in the study. Of those, 196 (53%) had RRMS, 92 (25%) SPMS, and 83 (22%) PPMS. Low FVC and FEV1 was present in 16 (8%), 16 (19%), and 23 (25%) of the patients in the RRMS, PPMS, and SPMS, respectively. PwMS with T2-FLAIR lesions involving the corpus callosum (CC) had a significantly higher frequency of abnormally low FVC and FEV1 (OR 3.62; 95% CI 1.33-9.83; p = 0.012) than patients without lesions in that region. This association remained significant in the RRMS group (OR 10.1; 95% CI 1.3-67.8; p 0.031) when the model excluded PPMS and SPMS. According to our study, for every increase of 1 z score of FVC, we observed an increase of 0.25 cm3 of hippocampal volume (β 0.25; 95% CI 0.03-0.47; p 0.023) and 0.43 cm3 of left hippocampus volume (β 0.43; 95% CI 0.16-0.71; p 0.002). We observed an incremental prevalence of abnormally low pulmonary function tests that parallels a sequence from more early relapsing courses to long-standing progressive courses (RRMS to PPMS or SPMS).

EPS6.09 Mid-term effect of elexacaftor/tezacaftor/ivacaftor on lung function in people with cystic fibrosis: real-world data of the German cystic fibrosis registry

Objectives: The aim of this observational cohort study is to report real-world data about short and mid-term effect of elexacaftor/tezacaftor/ivacaftor (ETI) on lung function in people with cystic fibrosis (pwCF).

Quantifying variation in home spirometry in people with cystic fibrosis during baseline health, and associations with clinical outcomes

BackgroundHome spirometry is increasingly used to monitor lung function in people with cystic fibrosis (pwCF). Although decreases in lung function in the setting of increased respiratory symptoms are consistent with a pulmonary exacerbation (PEx), the interpretation of home spirometry during asymptomatic periods of baseline health is unclear. The aims of this study were to determine the variation in home spirometry in pwCF during asymptomatic periods of baseline health and to identify associations between this variation and PEx. MethodsNear-daily home spirometry measurements were obtained from a cohort of pwCF enrolled in a long-term study of the airway microbiome. Associations between the degree of variation in home spirometry and the time to next PEx were evaluated. ResultsThirteen subjects (mean age of 29 years and mean percent predicted forced expiratory volume in one second [ppFEV1] of 60) provided a median of 204 spirometry readings taken during 40 periods of baseline health. The mean week-to-week within-subject level of variation in ppFEV1 was 15.2 ± 6.2%. The degree of variation in ppFEV1 during baseline health was not associated with time to PEx. ConclusionsVariation in ppFEV1 measured with near-daily home spirometry in pwCF during periods of baseline health exceeded the variation in ppFEV1 expected in clinic spirometry (based on ATS guidelines). The degree of variation in ppFEV1 during baseline health was not associated with time to PEx. These data are relevant for guiding interpretation of home spirometry.

Safety of elexacaftor/tezacaftor/ivacaftor dose reduction: Mechanistic exploration through physiologically based pharmacokinetic modeling and a clinical case series.

Elexacaftor/tezacaftor/ivacaftor (ETI) treatment is associated with significant improvement in lung function in people with cystic fibrosis (pwCF); however, some patients experience adverse effects (AEs) including hepatotoxicity. One potential strategy is dose reduction in ETI with the goal of maintaining therapeutic efficacy while resolving AEs. We report our experience of dose reduction in individuals who experienced AEs following ETI therapy. We provide mechanistic support for ETI dose reduction by exploring predicted lung exposures and underlying pharmacokinetics-pharmacodynamics (PK-PD) relationships. Adults prescribed ETI who underwent dose reduction due to the AEs were included in this case series, and their percent predicted forced expiratory volume in 1 s (ppFEV1 ) and self-reported respiratory symptoms were collected. The full physiologically based pharmacokinetic (PBPK) models of ETI were developed incorporating physiological information and drug-dependent parameters. The models were validated against available pharmacokinetic and dose-response relationship data. The models were then used to predict lung concentrations of ETI at steady-state. Fifteen patients underwent dose reduction in ETI due to AEs. Clinical stability without significant changes in ppFEV1 after dose reduction was observed in all patients. Resolution or improvement of AEs occurred in 13 of the 15 cases. The model-predicted lung concentrations of reduced dose ETI exceeded the reported half maximal effective concentration (EC50 ) from measurement of in vitro chloride transport, providing a hypothesis as to why therapeutic efficacy was maintained. Albeit in a small number of patients, this study provides evidence that reduced ETI doses in pwCF who have experienced AEs may be effective. The PBPK models enable exploration of a mechanistic basis for this finding by simulating target tissue concentrations of ETI that can be compared with drug efficacy in vitro.

Essential Fatty Acid Deficiency in Cystic Fibrosis Disease Progression: Role of Genotype and Sex.

Adequate intake of nutrients such as essential fatty acids (EFA) are critical in cystic fibrosis (CF). The clinical course of deterioration of lung function in people with CF has been shown to relate to nutrition. Independent of the higher energy consumption and malabsorption due to pancreatic insufficiency, EFA deficiency is closely associated with the risk of pulmonary infection, the most significant pathology in CF. This review will focus on the EFA deficiency identified in people with CF, as well as the limited progress made in deciphering the exact metabolic pathways that are dysfunctional in CF. Specifically, people with CF are deficient in linoleic acid, an omega 6 fatty acid, and the ratio of arachidonic acid (omega 6 metabolite) and docosahexaenoic acid (omega 3 metabolite) is increased. Analysis of the molecular pathways in bronchial cells has identified changes in the enzymes that metabolise EFA. However, fatty acid metabolism primarily occurs in the liver, with EFA metabolism in CF liver not yet investigated, indicating that further research is required. Despite limited understanding in this area, it is well known that adequate EFA concentrations are critical to normal membrane structure and function, and thus are important to consider in disease processes. Novel insights into the relationship between CF genotype and EFA phenotype will be discussed, in addition to sex differences in EFA concentrations in people with CF. Collectively, investigating the specific effects of genotype and sex on fatty acid metabolism may provide support for the management of people with CF via personalised genotype- and sex-specific nutritional therapies.

568 Association between antifungal use and lung function in people with cystic fibrosis and Aspergillus-positive cultures

568 Association between antifungal use and lung function in people with cystic fibrosis and Aspergillus-positive cultures

The Relationship Between BMI and Lung Function in Populations with Different Characteristics: A Cross-Sectional Study Based on the Enjoying Breathing Program in China.

PurposeTo analyze the relationship between body mass index (BMI) and lung function, which may help optimize the screening and management process for chronic obstructive pulmonary disease (COPD) in the early stages.Patients and MethodsIn this cross-sectional study using data from the Enjoying Breathing Program in China, participants were divided into two groups according to COPD Screening Questionnaire (COPD-SQ) scores (at risk and not at risk of COPD) and three groups based on lung function (normal lung function, preserved ratio impaired spirometry [PRISm], and obstructive lung function).ResultsA total of 32,033 subjects were enrolled in the current analysis. First, in people at risk of COPD, overweight and obese participants had better forced expiratory volume in one second (FEV1; overweight: 0.33 liters (l), 95% confidence interval [CI]: 0.27 to 0.38; obesity: 0.31 L, 95% CI: 0.22 to 0.39) values than the normal BMI group. Second, among people with PRISm, underweight participants had a lower FEV1 (−0.56 L, 95% CI: −0.86 to −0.26) and forced vital capacity (FVC; −0.33 L, 95% CI: −0.55 to −0.11) than participants with a normal weight, and obese participants had a higher FEV1 (0.22 L, 95% CI: 0.02 to 0.42) and FVC (0.16 L, 95% CI: 0.02 to 0.30) than participants with a normal weight. Taking normal BMI as the reference group, lower FEV1 (−0.80 L, 95% CI: −0.97 to −0.63) and FVC (−0.53 L, 95% CI: −0.64 to −0.42) were found in underweight participants with obstructive spirometry, and better FEV1 (obesity: 0.26 L, 95% CI: 0.12 to 0.40) was found in obese participants with obstructive spirometry.ConclusionBeing underweight and severely obese are associated with reduced lung function. Slight obesity was shown to be a protective factor for lung function in people at risk of COPD and those with PRISm.

Preoperative exercise training for people with non-small cell lung cancer.

Surgical resection for early-stage non-small cell lung cancer (NSCLC) offers the best chance of cure, but it is associated with a risk of postoperative pulmonary complications. It is unclear if preoperative exercise training, and the potential resultant improvement in exercise capacity, may improve postoperative outcomes. This review updates our initial 2017 systematic review. 1. To evaluate the benefits and harm of preoperative exercise training on postoperative outcomes, such as the risk of developing a postoperative pulmonary complication and the postoperative duration of intercostal catheter, in adults scheduled to undergo lung resection for NSCLC. 2. To determine the effect on length of hospital stay (and costs associated with postoperative hospital stay), fatigue, dyspnoea, exercise capacity, lung function and postoperative mortality. We used standard, extensive Cochrane search methods. The latest search date was from 28 November 2016 to 23 November 2021. We included randomised controlled trials (RCTs) in which study participants who were scheduled to undergo lung resection for NSCLC were allocated to receive either preoperative exercise training or no exercise training. We used standard Cochrane methods. Our primary outcomes were 1. risk of developing a postoperative pulmonary complication; 2. postoperative duration of intercostal catheter and 3. Our secondary outcomes were 1. postoperative length of hospital stay; 2. postintervention fatigue; 3. postintervention dyspnoea; 4. postintervention and postoperative exercise capacity; 5. postintervention lung function and 6. postoperative mortality. We used GRADE to assess the certainty of evidence for each outcome. Along with the five RCTs included in the original version, we identified an additional five RCTs, resulting in 10 RCTs involving 636 participants. Preoperative exercise training results in a large reduction in the risk of developing a postoperative pulmonary complication compared to no preoperative exercise training (risk ratio (RR) 0.45, 95% CI 0.33 to 0.61; I2 = 0%; 9 studies, 573 participants; high-certainty evidence). The evidence is very uncertain about its effect on postoperative intercostal catheter duration (MD -2.07 days, 95% CI -4.64 to 0.49; I2 = 77%, 3 studies, 111 participants; very low-certainty evidence). Preoperative exercise training is likely safe as studies reported no adverse events. Preoperative exercise training likely results in a reduction in postoperative length of hospital stay (MD -2.24 days, 95% CI -3.64 to -0.85; I2 = 85%; 9 studies, 573 participants; moderate-certainty evidence). Preoperative exercise training likely increases postintervention exercise capacity measured by peak oxygen consumption (MD 3.36 mL/kg/minute, 95% CI 2.70 to 4.02; I2 = 0%; 2 studies, 191 participants; moderate-certainty evidence); but the evidence is very uncertain about its effect on postintervention exercise capacity measured by the 6-minute walk distance (MD 29.55 m, 95% CI 12.05 to 47.04; I2 = 90%; 6 studies, 474 participants; very low-certainty evidence). Preoperative exercise training may result in little to no effect on postintervention lung function (forced expiratory volume in one second: MD 5.87% predicted, 95% CI 4.46 to 7.28; I2 = 0%; 4 studies, 197 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Preoperative exercise training results in a large reduction in the risk of developing a postoperative pulmonary complication compared to no preoperative exercise training for people with NSCLC. It may also reduce postoperative length of hospital stay, and improve exercise capacity and lung function in people undergoing lung resection for NSCLC. The findings of this review should be interpreted with caution due to risk of bias. Research investigating the cost-effectiveness and long-term outcomes associated with preoperative exercise training in NSCLC is warranted.

Persistent Aspergillus fumigatus infection in cystic fibrosis: impact on lung function and role of treatment of asymptomatic colonization—a registry-based case–control study

BackgroundAspergillus fumigatus is the most common filamentous fungus isolated from the airways of people with cystic fibrosis (CF). The aim of this study was to investigate how chronic A. fumigatus colonization affects lung function in people with CF, to identify risk factors for colonization, and to evaluate antifungal treatment of asymptomatic Aspergillus colonization.MethodsData from 2014–2018 was collected from the Swedish CF registry and medical records. Baseline data before the start of A. fumigatus colonization was compared with the two succeeding years to evaluate how colonization and treatment affected lung function and other clinical aspects.ResultsA total of 437 patients were included, of which 64 (14.6%) became colonized with A. fumigatus during the study period. Inhaled antibiotics was associated with A. fumigatus colonization (adjusted OR 3.1, 95% CI 1.6–5.9, p < 0.05). Fungal colonization was not associated with a more rapid lung function decline or increased use of IV-antibiotics compared to the non-colonized group, but patients with A. fumigatus had more hospital days, a higher increase of total IgE, and higher eosinophil counts. In the Aspergillus group, 42 patients were considered to be asymptomatic. Of these, 19 patients received antifungal treatment. Over the follow up period, the treated group had a more pronounced decrease in percent predicted Forced Expiratory Volume in one second (ppFEV1) compared to untreated patients (− 8.7 vs − 1.4 percentage points, p < 0.05).ConclusionInhaled antibiotics was associated with A. fumigatus colonization, but no association was found between persistent A. fumigatus and subsequent lung function decline. No obvious benefits of treating asymptomatic A. fumigatus colonization were demonstrated.

WS07.01 Investigating the effects of dornase alfa and hypertonic saline used in combination on lung function in people with cystic fibrosis

WS07.01 Investigating the effects of dornase alfa and hypertonic saline used in combination on lung function in people with cystic fibrosis

Effects of Air Pollution on the Development of Respiratory Diseases among Residents in New Delhi, India

Air pollution is the contamination of the indoor or outdoor environment by any chemical, physical or biological agent that modifies the natural characteristics of the atmosphere. The industrialization of countries has increased the emission to the atmosphere that has significantly oplurid the air. Exposure to high levels of air pollution can cause a variety of adverse health outcomes. Hence, the study sought to examine the effects of air pollution on the development of respiratory diseases among residents in New Delhi, India. The study adopted the descriptive research design. The targeted population included the residents of New Delhi. The key respondents included health practitioners. The collection of the data was done using the questionnaires. The rationale for picking the health practitioners to respond to the research instruments is because they were more involved in the treatment and were more informed about the cases that have been reported from the residents due to the air pollution. The study found that air pollution positively influences the development of respiratory diseases. Air pollution can worsen lung function in people with breathing problems and decrease lung function in those with healthy lungs. Exposure to air pollution puts you at risk for lung cancer, heart attacks, stroke and, in extreme cases, premature death. The study concluded that air pollution is a danger to lung health, particularly for children, the elderly, people who work or spend time outdoors and people with heart or lung disease. The study recommended strict measures/initiatives should be taken by the government, industry and the private sector to reduce the burden of air pollution. It is further recommended that individuals should use clean fuels. Likewise, air cleansers that can enhance the air quality are suggested. Industrialization, urbanization, population growth and demand for transportation, mainly in the cities, need to be managed. Keywords: Air Pollution, Respiratory Health Complications, New Delhi, India

Association Between Serum Uric Acid and Lung Function in People with and without Chronic Obstructive Pulmonary Disease.

BackgroundThe effect of serum uric acid (SUA) levels on lung function in chronic obstructive pulmonary disease (COPD) people remained unclear. We aimed to investigate the association between SUA and lung function.MethodsA cross-sectional study was performed to measure the SUA levels and lung function in 2797 consecutive eligible individuals. Of these, individuals in our study were divided into two groups, the COPD group (n=1387) and the non-COPD group (n=1410). The diagnosis of COPD is defined as post-bronchodilator first second of forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio of less than 0.70. Multivariable adjustment linear models were applied to estimate the effect of SUA levels on FEV1% predicted, FVC% predicted, and FEV1/FVC stratified by COPD status.ResultsAfter multivariable adjustment, each 1 mg/dL increase of SUA was significantly associated with a decrease in FEV1% predicted (−1.63%, 95% confidence interval [CI] −2.37 to −0.90), FVC % predicted (−0.89%, 95% CI −1.55 to −0.24), and FEV1/FVC (−0.70%, 95% CI −1.10 to −0.30). In the COPD group, each 1 mg/dL increase of SUA was significantly associated with decreases in FEV1% predicted (−1.87%, 95% CI −2.91 to −0.84), FVC% predicted (−1.35%, 95% CI −2.35 to −0.34), and FEV1/FVC (−0.63%, 95% CI −1.18 to −0.08). However, no significant association between lung function and SUA was found among people without COPD.ConclusionHigh SUA levels were associated with lower lung function, especially in COPD patients. However, no statistically significant effect of SUA on lung function was found in people without COPD.