Decreased Lung Function Research Articles

Body mass index trajectories from birth to early adulthood and lung function development.

Limited studies have investigated the influence of body mass index (BMI) trajectories on lung function covering the entire growth period. We conducted a prospective study utilizing data from the Swedish BAMSE birth cohort. Latent class mixture modelling was employed to examine the diversity in BMI z-scores from birth to 24 years of age. Participants with four or more BMI z-scores were included (n=3204, 78·4%). Pre-bronchodilator (BD) spirometry was tested at 8, 16, and 24 years, while post-BD spirometry, multiple-breath nitrogen washout (for lung clearance index, LCI), and urinary metabolomics data were assessed at 24 years. Six distinct BMI development groups were identified. Compared to the stable normal BMI group, the accelerated increasing BMI group exhibited reduced pre- and post-BD FEV1/FVC ratio z scores (β=-0·26, 95% CI=[-0·44, -0·08], and -0·22, [ -0·39, -0·05], respectively), along with elevated LCI (0·30, [0·22, 0·42]) at 24 years. The persistent high BMI group demonstrated lower FEV1, and FVC z scores growth between 16 and 24 years (-0.24, [-0.42, -0.05], and -0.27, [-0.45, -0.01], respectively), and elevated LCI (0·20, [0·03, 0·39]) at 24 years. However, those impairments were not observed in the accelerated resolving BMI group. Conversely, the persistent low BMI group displayed persistently decreased FEV1, and FVC from 8 to 24 years, as well as decreased lung function growth. Additionally, histidine-related metabolites were associated with pre- and post-BD FEV1 (hypergeometric FDR=0.008 and <0.001, respectively). Early interventions aiming for normal BMI during childhood may contribute to improved lung health later in life.

Exploring the correlation between body mass index and lung function test parameters: a cross-sectional analytical study

PurposeThe correlation between body weight and health is a significant public health concern. While the adverse effects of obesity on pulmonary function are well-known, the impact of being underweight remains debated due to limited research. This study aimed to investigate the correlation between Body Mass Index (BMI) categories and lung function parameters.ResultsA study of 3077 participants found significant differences in gender, age, height, and weight across various Body Mass Index (BMI) categories. The study found non-significant variations in forced expiratory flow (FVC) across BMI categories, with underweight individuals showing lower FVC compared to normal and overweight individuals. BMI significantly impacted mean forced expiratory flow during the middle half of FVC. A significant negative correlation was observed between age and FVC, FEV1, FEV1/FVC ratio, and FEF25-75. A significant positive correlation was observed between weight, height, and lung function parameters. Multiple regression analysis revealed a decrease in lung function with advancing age, while height showed significant positive associations. The study concluded that age, sex, smoking, height, and weight collectively explained 41.0% of the variance in FVC, FEV, and FEF25-75.

Bronchiectasis Exacerbations: Are We Doing Everything We Can?

At the European Respiratory Society (ERS) Congress 2024, two experts in bronchiectasis, Pieter Goeminne, Department of Respiratory Diseases, Vitaz Saint-Nicholas Hospitals, Belgium, and Michal Shteinberg, Pulmonology Institute and CF Center – Carmel Medical Center; Israel Institute of Technology; and The B. Rappaport Faculty of Medicine, Haifa, Israel, discussed bronchiectasis’ pathogenesis and exacerbations, along with unmet needs regarding diagnosis and treatment. Bronchiectasis is a chronic and progressive inflammatory disease with a rising prevalence. Commonly associated conditions/related comorbidities of bronchiectasis include post-infective diseases and other airway conditions (such as chronic obstructive pulmonary disease [COPD] and asthma), although the cause of bronchiectasis may remain unknown in over a third of patients. Development of bronchiectasis involves the intersection of four pathogenic components: chronic infections, airway ciliary dysfunction, chronic inflammation (mostly neutrophilic), and structural lung damage, commonly known as the ‘vicious vortex.’ In particular, bronchiectasis development, progression, and exacerbation also involve upregulated and dysregulated neutrophil function. Exacerbations in bronchiectasis are marked by symptoms of increased cough, sputum changes, decreased lung function, and fatigue, among others. Careful clinical examination and awareness of bronchiectasis symptoms are needed to properly diagnose and treat the initial condition and prevent exacerbations. Triggers for exacerbations can be endogenous, such as neutrophil or eosinophil increases, as well as exogenous, including the presence of infectious agents and pollution. Research regarding treatment for bronchiectasis is limited, but European guidelines recommend airway clearance techniques and antibiotics during exacerbations. To enable more targeted treatment for bronchiectasis from first occurrence, to limit exacerbations, and during an exacerbation, there are unmet needs for better identification of resistant genes, treatments for pathogens and inflammation, and biomarkers of exacerbation triggers.

Functional Lung Disorders in Smoking Patients with Pulmonary Tuberculosis

Introduction. There is evidence that smoking affects the course and effectiveness of treatment of patients with pulmonary tuberculosis. At the same time, tobacco smoking and pulmonary tuberculosis are significant risk factors in the development of functional lung disorders.The purpose of the study to study the nature of changes in spirometry parameters and the peculiarities of the course of the tuberculosis process in smoking patients.Materials and methods. A retrospective cohort study, which included 102 patients with pulmonary tuberculosis. The patients were divided into two groups: 1 — smoking patients (47 people), 2 — non-smoking patients (55 people).Results. It is shown that men are significantly more common among the former, while women are more common among the latter (p = 0.001). Bilateral lung tissue lesions are more common among smokers compared to non-smokers. It is shown that a decrease in the volume of forced exhalation in the first second (OFV1) of an extremely severe degree is significantly more often observed among smokers (p = 0.028). At the same time, a mild degree is more common among non-smokers (p = 0.039).Discussion. Thus, the most important problem among smokers and non-smokers is a violation of the functional parameters of the lungs. Currently, there is a need to find optimal approaches to prevent a decrease in lung function. Conclusion. It has been shown that a decrease in lung function is observed more often among smoking patients. Also, respiratory symptoms and infiltrative pulmonary tuberculosis are more common among smokers compared to non-smokers.

Non-dietary exposure to phthalates in primary school children: Risk and correlation with anthropometric indices, cardiovascular and respiratory diseases

Phthalates are endocrine disruptors of increasing concern for human health; however, previous studies have only assessed the association between internal exposure and human health. We aimed to assess the non-carcinogenic and carcinogenic risks of non-dietary exposure to phthalates in indoor environments among primary school children and their correlations with health indicators. A study involving 54 children was conducted in Jinan, Shandong Province, China. Questionnaires and health examinations were conducted, dust in hard-to-clean corners of students’ classrooms and homes was collected, and airborne phthalates in the middle of classrooms and family living rooms were sampled. The gas-phase phthalate concentrations, individual exposure, and non-carcinogenic and carcinogenic risks were calculated. Associations were estimated using linear mixed models. The findings revealed that phthalates posed a non-carcinogenic risk to 7.4 % of the children and a moderate carcinogenic risk to 27.8 % of the children, with higher non-carcinogenic and carcinogenic risks to girls than to boys. Five phthalates were negatively correlated with body mass index, dimethyl phthalate and diethyl phthalate (DEP) were significantly correlated with waist circumference, and di-iso-butyl phthalate (DiBP) was negatively correlated with hip circumference. DiBP, di-n-butyl phthalate, and DEP, were significantly correlated with cardiovascular disease, DEP and di (2-n-butoxyethyl) phthalate were correlated with decreased lung function, and di-n-octyl phthalate influenced airway inflammation. The findings indicated that phthalate exposure may negatively impact children's health, thereby warranting further comprehensive research on the health effects of these chemicals.

Effects of single and combined urinary polycyclic aromatic hydrocarbon effects on lung function in the U.S. adult population

BackgroundThe impact of polycyclic aromatic hydrocarbons (PAHs) on lung function has garnered attention, but studies mostly focus on individual effect. This study investigates urinary PAH metabolites as biomarkers of exposure and assesses the relationships between single and combined exposures to nine urinary PAH metabolites and lung function in adults.MethodsData from 4040 adults in the 2007–2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. Weighted generalized linear models estimated the effects of individual PAH metabolites on lung function. Additionally, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were employed to evaluate the combined impacts of multiple PAH metabolites.ResultsAnalyses of individual PAH metabolites revealed negative associations with lung function, excluding forced vital capacity (FVC). The WQS, qgcomp, and BKMR models consistently showed that exposure to multiple PAH metabolites was associated with lung function decrease. WQS indicated that 2-hydroxynaphthalene (2-NAP) was the largest contributor to the reductions in forced expiratory volume in 1 s (FEV1), FVC, peak expiratory flow (PEF), and forced expiratory flow from 25 to 75% of FVC (PEF25-75%). Additionally, 1-hydroxypyrene (1-PYR) was the primary PAH metabolite contributing to the decreases in FEV1/FVC and fractional exhaled nitric oxide (FeNO). The combined effect of urinary PAH metabolites did not affect FVC in the current smokers or FeNO in nonsmokers, but decreased FEV1/FVC in current smokers.ConclusionThis study strengthens the negative relationships between multiple PAH metabolites exposure and lung function in adults. Given the limitations of this study, including the lack of knowledge of other exposure pathways and the uncertainty of urinary metabolites, further research is necessary to explore the mechanisms underlying these associations and to address the limitations in exposure assessment.

Integrating Real-Time Air Quality Monitoring, Ecological Momentary Assessment, and Spirometry to Evaluate Asthma Symptoms: Usability Study.

Individuals are exposed to a variety of indoor residential toxins including volatile organic compounds and particulates. In adults with asthma, such exposures are associated with asthma symptoms, asthma exacerbations, and decreased lung function. However, data on these exposures and asthma-related outcomes are generally collected at different times and not in real time. The integration of multiple platforms to collect real-time data on environmental exposure, asthma symptoms, and lung function has rarely been explored. This paper describes how adults with asthma perceive the acceptability and usability of three integrated devices: (1) residential indoor air quality monitor, (2) ecological momentary assessment (EMA) surveys delivered via a smartphone app, and (3) home spirometry, over 14 days. Participants (N=40) with uncontrolled asthma were mailed the Awair Omni indoor air quality monitor, ZEPHYRx home spirometer, and detailed instructions required for the in-home monitoring. The air quality monitor, spirometer, and EMA app were set up and tested during a videoconference or phone orientation with a research team member. Midway through the 14-day data collection period, participants completed an interview about the acceptability of the study devices or apps, instructional materials provided, and the setup process. At the end of the 14-day data collection period, participants completed a modified System Usability Scale. A random sample of 20 participants also completed a phone interview regarding the acceptability of the study and the impact of the study on their asthma. Participants ranged in age from 26 to 77 (mean 45, SD 13.5) years and were primarily female (n=36, 90%), White (n=26, 67%), college graduates (n=25, 66%), and residing in a single-family home (n=30, 75%). Most indicated that the air quality monitor (n=23, 58%), the EMA (n=20, 50%), and the spirometer (n=17, 43%) were easy to set up and use. Challenges with the EMA included repetitive surveys, surveys arriving during the night, and technical issues. While the home spirometer was identified as a plausible means to evaluate lung function in real time, the interpretation of the readings was unclear, and several participants reported side effects from home spirometer use. Overall, the acceptability of the study and the System Usability Scale scores were high. The study devices were highly acceptable and usable. Participant feedback was instrumental in identifying technical challenges that should be addressed in future studies.

The lung proteome in HIV-associated obstructive lung disease (OLD)

RationaleObstructive lung disease is increasingly common among persons living with HIV (PLWH). There are currently no validated biomarkers that identify individuals at risk of developing obstructive lung disease (OLD) and specific mechanisms contributing to HIV-associated OLD remain elusive, independent of smoking.ObjectivesWe sought to identify biomarkers and biological pathways associated with OLD using a broad proteomic approach.MethodsWe performed tandem mass tagging and mass spectrometry (MS) analysis on bronchoalveolar lavage fluid (BALF) samples from persons living with HIV with OLD (n=26) and without OLD (n=26). We combined untargeted MS with a targeted SomaScan aptamer-based approach. We used Pearson correlation tests to identify associations between each protein and lung function (FEV1pp). We adjusted for multiple comparisons using a false discovery rate (FDR) adjustment. Significant proteins were entered into a pathway overrepresentation analysis. Protein-driven endotypes were constructed using K-means clustering.Measurements and main resultsWe identified over 3800 proteins by MS and identified 254 proteins that correlated with FEV1pp when we combined the MS and SomaScan proteomes when adjusting for smoking status. Pathway analysis revealed cell adhesion molecules as significant.ConclusionsProtein expression differs in the lung of PWH and decreased lung function (FEV1pp). Pathway analysis reveals cell adhesion molecules having potentially important roles in this process.

Outcomes and predictors of progression in progressive pulmonary fibrosis

Background Progressive pulmonary fibrosis (PPF) is a general term for a class of interstitial lung diseases (ILDs) characterized by a progressive fibrosing (PF) phenotype. Patients with PPF have decreased lung function, exercise ability, and quality of life. The purpose of this study was to investigate the clinical characteristics, potential associated factors for disease progression, and survival outcomes of patients in the PPF population. Methods This study retrospectively reviewed the data of patients diagnosed with ILD between January 2011 and December 2022 at The First Affiliated Hospital of Ningbo University. A PF phenotype was defined based on the criteria that were used in the PPF clinical practice guidelines, which led to the identification of 92 patients with a PF phenotype among the 177 patients with fibrotic ILD. Baseline clinical information and laboratory parameters were collected and analysed in our cohort. Results Patients in the PPF group had higher tumour marker levels and lower pulmonary function test results at baseline than did those in the non-PPF group. According to the multivariate logistic regression analysis, age >65 years (OR 2.71, 95% CI 1.26-5.89; p = 0.011), LDH >245 U/L (OR 3.07, 95% CI 1.39-6.78; p = 0.006), CA-153 > 35 U/mL (OR 3.16, 95% CI 1.25-7.97; p = 0.015), FVC <60% predicted (OR 4.82, 95% CI 1.60-14.51; p = 0.005), DLCO <50% predicted (OR 3.21, 95% CI 1.43-7.21; p = 0.005), and the UIP-like pattern on chest HRCT (OR 3.65, 95% CI 1.33-10.07; p = 0.012) were potentially associated with the progression of fibrotic interstitial lung diseases (f-ILDs) to PPF. Furthermore, the PPF group had a poorer survival rate than the non-PPF group (p = 0.0045). According to the multivariate Cox regression analysis, an SPAP ≥ 37 mmHg (HR 2.33, 95% CI 1.09-5.00; p = 0.030) and acute exacerbation (HR 2.88, 95% CI 1.26-6.59; p = 0.012) were identified as significant prognostic factors for mortality in patients with PPFs. Conclusions Patients who were older, had high CA-153 and LDH levels, had poor pulmonary function test results, or had a UIP-like pattern on chest HRCT were more likely to have indications for the progression of f-ILD to PPF. Increased SPAP and AE are independent risk factors for the prognosis of PPF patients, so additional attention should be given to such patients.

Lung-Kidney Axis in Cystic Fibrosis: Early Urinary Markers of Kidney Injury Correlate with Neutrophil Activation and Worse Lung Function.

Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF. Urinary total protein, albumin, and markers of kidney injury and neutrophil activation, normalized to creatinine, as well as urinary immune cells, were quantified in CF (n = 48) and healthy (n = 33) cohorts. Infection burden and chronicity were defined by sputum culture and serum titers of anti-bacterial antibodies. PwCF had increased urinary protein levels, consisting of low-molecular-weight tubular injury markers, independent of glomerular filtration rate (eGFR). This finding suggests subclinical renal injury processes. Urinary analysis of the CF cohort identified different associations of urinary injury markers with aminoglycoside exposure, lung function, and neutrophil activation. High urinary KIM-1 levels and increased prevalence of neutrophils among urine immune cells correlated with decreased lung function in PwCF. The relationship between tubular injury and decreased lung function was most prominent in patients harboring chronic Pseudomonas aeruginosa infection. Increased urinary tubular injury markers in PwCF suggest early subclinical renal injury not readily detected by eGFR. The strong association of high urinary KIM-1 and neutrophils with diminished lung function and high Pseudomonas aeruginosa burden suggests that pulmonary disease may contribute to renal injury in CF.

Determinants of Pneumonia Status in Under-five Children in Indonesia

Background: Pneumonia is a communicable disease that causes the largest under-five children death in the world. Meanwhile, Indonesia contributed 19.000 cases of under-five deaths due to pneumonia in 2018. Pneumonia can inhibit the growth and development in under-five children, cause decreased lung function or even lead to death. The pneumonia symptoms is less specific and almost the same as the flu or a common cough, makes this disease difficult to detect and difficult to treat optimally. This study was aimed to determine variables that affect the pneumonia in under-five children in Indonesia in 2018.Methods: This study used descriptive analysis and multilevel binary logistic regression. It used secondary data from the Riskesdas 2018, publication of Profil Kesehatan Indonesia 2018, and official website of Badan Pusat StatistikResult: The results indicated that in 2018, there were about 6.4 percent of under-five children who experienced pneumonia. The age of under-five children, gender, nutritional status, maternal education level, type of residence, house’s ventilation, and poverty rate per province significantly affected the status of pneumonia in under-five children in Indonesia.Conclusion : This study was expected to be able to increase public awareness about pneumonia in under-five children and can prevent under-five deaths due to pneumonia. Further research can use more up-to-date primary data and can also focus on provinces that have high rates of pneumonia in under-five children.

Analisis Putusan Pengadilan dalam Perkara Tindak Pidana Pencemaran Udara

Air pollution is one part of physical environmental pollution. Air pollution according to the Government Regulation on air pollution control is the entry or introduction of substances, energy, and/or other components into ambient air by human activities, so that the quality of ambient air decreases to a certain level that causes ambient air to be unable to fulfill its function. The research method used is to use a type of normative legal research method, by examining library materials or secondary data which include primary legal materials, secondary legal materials and tertiary legal materials using Decision Number 68/Pdt.G/LH/2022/PN Rap. The results of the study, namely the lawsuit was rejected by the Court and the impact was air pollution, namely respiratory disorders, cardiovascular disease, impaired fetal development, decreased lung function, and chronic diseases. Conclusion Air is very important because it provides oxygen and other gases that are essential for all life on earth. Air pollution or contamination is the introduction of other components into the air, either by human activities directly or indirectly or due to natural processes. The impacts of this pollution include respiratory disorders, cardiovascular disease, impaired fetal development, decreased lung function, and chronic diseases. Suggestions Palm oil mills need to adopt more effective pollution control technologies to reduce emissions of hazardous materials into the air. Local governments and environmental regulatory agencies must ensure that palm oil mills comply with all applicable environmental regulations and standards. Local communities must be empowered and educated about their rights and how to advocate for a healthy environment.

Associations of dietary inflammation index and composite dietary antioxidant index with preserved ratio impaired spirometry in US adults and the mediating roles of triglyceride-glucose index: NHANES 2007–2012

BackgroundPrevious studies have shown that inflammatory and antioxidant dietary patterns can modify the risk of COPD, yet few studies have examined the association of these diets with its early signs (PRISm), and the potential role of metabolic disorders remains to be elucidated. MethodsData from 9529 individuals who participated in the 2007–2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. The Dietary Inflammation Index (DII) and the Dietary Antioxidant Composite Index (CDAI) were assessed using 24-h dietary recall, multiple metabolic indicators were calculated according to biochemical markers, and lung function parameters defined PRISm cases. Individual and joint effects of DII and CDAI were evaluated by generalized linear models and binary logistic regression models, and mediation effects of metabolic indicators were further explored by causal mediation analysis. ResultsIncreased DII was associated with decreased lung function (FEV1: β = −18.82, FVC: β = −29.2; OR = 1.04) and increased metabolic indicators (β = 0.316, 0.036, 0.916, 0.033, and 0.145 on MAP, UA, TC, TyG, and MS, respectively). Contrary to this, CDAI were positively and negatively associated with lung function (FEV1: β = 3.42; FVC: β = 4.91; PRISm: OR = 0.99) and metabolic indicators (β < 0), respectively. Joint effects of DII and CDAI indicated the minimal hazard effects of DII on TyG (β = −0.11), FEV1 (β = 72.62), FVC (β = 122.27), and PRISm (OR = 0.79) in subjects with high CDAI when compared with those with low CDAI (low DII + high CDAI vs. high DII + low CDAI). Furthermore, TyG mediated 13.74 %, 8.29 %, and 21.70 % of DII- and 37.30 %, 20.90 %, and 12.32 % of CDAI-FEV1, -FVC, and -PRISm associations, respectively. ConclusionsThese findings indicated that CDAI can attenuate the adverse effects of DII on metabolic disorders and lung function decline, which provides new insight for diet modification in preventing early lung dysfunction.

Recurrent Infected Bronchiectasis in Poorly Controlled Patient Leading to Cardio Hepatorenal Syndrome

Background: Cardio hepatorenal syndrome is a severe condition due to chronic congestive heart failure complications characterized by liver and kidney function impairment, however, this condition has a potentially reversible complication.Bronchiectasis as a chronic lung disease was a burden for the healthcare system, especially involving other organs like heart, liver, and renal function. Those conditions were complicated and created a quandary regarding the effective treatments to improve the clinical condition and reduce morbidity and mortality. Case illustration: A 42-year-old man developed cardio hepatorenal syndrome (CHRS), which may have occurred from recurrent infected bronchiectasis that he had. His HRCT scan of the thorax with contrast showed multiple dilated bronchiwith tram track and signet ring appearance with decreased liver and renal function in laboratory findings, and probability of pulmonary hypertension (PH) and right heart failure (RHF) in echocardiography examination. The diuretic, beta-blocker, and antibiotics were given. During hospitalization, there was improvement day by day not only in his clinical condition but also in his liver and renal function. He has used oxygen as needed, and there was no longer any indication for him to be hospitalized. Conclusion: Patients with chronic lung diseases like bronchiectasis could have decreased lung function, which developed into other connected organ functions, like heart, liver, and renal. In this case, we found reduced heart, liver, and renal function, requiring a multidisciplinary approach to improve the condition.

Potential of phosphodiesterase 4B inhibitors in the treatment of interstitial lung disease associated with autoimmune diseases.

Patients with autoimmune disease-related interstitial lung disease may develop pulmonary fibrosis, which may become progressive. Progressive pulmonary fibrosis (PPF) is associated with poor outcomes. Antifibrotic therapies have shown efficacy as treatments for PPF in patients with autoimmune diseases, but new treatments are needed to slow or halt disease progression. Phosphodiesterases (PDEs) are enzymes that mediate the hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Pre-clinical data suggest that preferential inhibition of PDE4B has the potential to slow the progression of pulmonary fibrosis by inhibiting inflammatory and fibrotic pathways, with a lower risk of gastrointestinal adverse events than associated with pan-PDE4 inhibitors. Nerandomilast (BI 1015550) is a preferential PDE4 inhibitor that has demonstrated anti-inflammatory and antifibrotic effects in pre-clinical studies. In a phase II trial in patients with idiopathic pulmonary fibrosis, nerandomilast (given alone or on top of background antifibrotic therapy) prevented a decrease in lung function over 12 weeks with an acceptable safety and tolerability profile. The phase III FIBRONEER-ILD trial is evaluating the efficacy and safety of nerandomilast, given alone or on top of nintedanib, in patients with PPF, including PPF associated with autoimmune diseases. In this article, we review the potential of PDE4B inhibition in the treatment of ILD associated with autoimmune diseases, including the pre-clinical and early clinical data available to date.

A lactobacilli-based inhaled live biotherapeutic product attenuates pulmonary neutrophilic inflammation

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature characterized by firmicute depletion. However, the relationship between pulmonary bacteria and the mechanisms of downstream disease development has yet to be elucidated. We hypothesized that murine models of BPD would show heightened acetylated proline-glycine-proline (Ac-PGP) pathway and neutrophil activity, and through gain- and loss-of-function studies we show that Ac-PGP plays a critical role in driving BPD development. We further test a inhaled live biotherapeutic (LBP) using active Lactobacillus strains in in vitro and in vivo models of BPD and COPD. The Lactobacillus-based LBP is effective in improving lung structure and function, mitigating neutrophil influx, and reducing a broad swath of pro-inflammatory markers in these models of chronic pulmonary disease via the MMP-9/PGP (matrix metalloproteinase/proline-glycine-proline) pathway. Inhaled LBPs show promise in addressing common pathways of disease progression that in the future can be targeted in a variety of chronic lung diseases.

Fibroblast-derived extracellular vesicles contain SFRP1 and mediate pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal chronic lung disease characterized by aberrant intercellular communication, extracellular matrix deposition, and destruction of functional lung tissue. While extracellular vesicles (EVs) accumulate in the IPF lung, their cargo and biological effects remain unclear. We interrogated the proteome of EV and non-EV fractions during pulmonary fibrosis and characterized their contribution to fibrosis. EVs accumulated 14 days after bleomycin challenge, correlating with decreased lung function and initiated fibrogenesis in healthy precision-cut lung slices. Label-free proteomics of bronchoalveolar lavage fluid EVs (BALF-EVs) collected from mice challenged with bleomycin or control identified 107 proteins enriched in fibrotic vesicles. Multiomic analysis revealed fibroblasts as a major cellular source of BALF-EV cargo, which was enriched in secreted frizzled related protein 1 (SFRP1). Sfrp1 deficiency inhibited the activity of fibroblast-derived EVs to potentiate lung fibrosis in vivo. SFRP1 led to increased transitional cell markers, such as keratin 8, and WNT/β-catenin signaling in primary alveolar type 2 cells. SFRP1 was expressed within the IPF lung and localized at the surface of EVs from patient-derived fibroblasts and BALF. Our work reveals altered EV protein cargo in fibrotic EVs promoting fibrogenesis and identifies fibroblast-derived vesicular SFRP1 as a fibrotic mediator and potential therapeutic target for IPF.

Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease.

The objective of this study was to investigate the relationship between low attenuation area (LAA) scores, pulmonary function parameters, and clinical prognosis in patients with chronic obstructive pulmonary disease (COPD). COPD patients were divided into four LAA-based grades. Various lung function parameters were measured and correlated with LAA scores. Patient symptoms were examined using the St. George's Respiratory Questionnaire (SGRQ) and exercise capacity using the 6-min walk test (6MWT). Statistical analysis determined the significance of differences. Higher levels of LAA were associated with decreased lung function and airflow limitations, suggesting a positive relationship between the two. Clinical symptom scores increased as COPD severity based on LAA stratification worsened. Reduced exercise capacity was shown by a substantial decline in 6MWT scores as COPD severity increased. As LAA scores increased, SGRQ scores increased, indicating a decreased quality of life (QOL). The study demonstrated a relationship between LAA scores and COPD severity. High LAA scores were associated with poor lung function, worse clinical symptoms, limited exercise capacity, and lower QOL. These findings show that LAA scores are clinically relevant for disease severity assessment and COPD management. Further research is required to determine LAA scores' prognostic significance in disease progression and treatment response to enhance COPD therapy.

Co-exposure effects of urinary polycyclic aromatic hydrocarbons and metals on lung function: mediating role of systematic inflammation

BackgroundPolycyclic aromatic hydrocarbons (PAHs) and metals were associated with decreased lung function, but co-exposure effects and underlying mechanism remained unknown.MethodsAmong 1,123 adults from National Health and Nutrition Examination Survey 2011–2012, 10 urinary PAHs, 11 urinary metals, and peripheral white blood cell (WBC) count were determined, and 5 lung function indices were measured. Least absolute shrinkage and selection operator, Bayesian kernel machine regression, and quantile-based g-computation were used to estimate co-exposure effects on lung function. Mediation analysis was used to explore mediating role of WBC.ResultsThese models demonstrated that PAHs and metals were significantly associated with lung function impairment. Bayesian kernel machine regression models showed that comparing to all chemicals fixed at median level, forced expiratory volume in 1 s (FEV1)/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25 and 75% decreased by 1.31% (95% CI: 0.72%, 1.91%), 231.62 (43.45, 419.78) mL/s, and 131.64 (37.54, 225.74) mL/s respectively, when all chemicals were at 75th percentile. In the quantile-based g-computation, each quartile increase in mixture was associated with 104.35 (95% CI: 40.67, 168.02) mL, 1.16% (2.11%, 22.40%), 294.90 (78.37, 511.43) mL/s, 168.44 (41.66, 295.22) mL/s decrease in the FEV1, FEV1/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25% and 75%, respectively. 2-Hydroxyphenanthrene, 3-Hydroxyfluorene, and cadmium were leading contributors to the above associations. WBC mediated 8.22%-23.90% of association between PAHs and lung function.ConclusionsCo-exposure of PAHs and metals impairs lung function, and WBC could partially mediate this relationship. Our findings elucidate co-exposure effects of environmental mixtures on respiratory health and underlying mechanisms, suggesting that focusing on highly prioritized toxicants would effectively attenuate adverse effects.

Moderate-intensity physical activity reduces the role of serum PFAS on COPD: A cross-sectional analysis with NHANES data.

Chronic obstructive pulmonary disease (COPD) has emerged as a leading cause of chronic disease morbidity and mortality globally, posing a substantial public health challenge. Perfluoroalkyl substances (PFAS) are synthetic chemicals known for their high stability and durability. Research has examined their potential link to decreased lung function. Physical activity (PA) has been identified as one of the primary modalities of the non-pharmacological treatment of COPD. To investigate the relationship between PFAS and COPD, and whether physical activity could reduce the risk of COPD caused by PFAS exposure, we used data from the NHANES 2013-2018, a cross-sectional study. Logistic regression analysis was used to examine the associations between PFAS and COPD in adult populations, and their associations in different PA types. We finally included 4857 participants in the analysis, and found that Sm-PFOS (OR: 1.250), PFOA (OR: 1.398) and n-PFOA (OR: 1.354) were closely related to COPD; After stratified by gender, age and smoking, the results showed that Sm-PFOA (OR: 1.312) was related to COPD in female adult, and PFOA (OR: 1.398) and n-PFOA (OR: 1.354) were associated with COPD in male adults; The associations of Sm-PFOS (OR: 1.280), PFOA (OR: 1.481) and n-PFOA (OR: 1.424)with COPD tended to be stronger and more consistent in over 50 years old adults; Sm-PFOS was related to COPD in current smoker (OR: 1.408), and PFOA was related to COPD in former smoker (OR: 1.487); Besides, in moderate-intensity PA group, there were no associations of Sm-PFOS, PFOA and n-PFOA with COPD stratified by gender, age and smoking. PFAS exposure may increase the risk of developing COPD, but regular moderate-intensity physical activity can protect individuals from evolving to the disease. However, longitudinal studies are needed to support these preliminary findings.