Worse Lung Function Research Articles

Aspergillus serology and clinical outcomes in patients with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC)

IntroductionAspergillus sp. cause diverse clinical manifestations in bronchiectasis including Allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS) and raised IgG indicating exposure or infection with Aspergillus. Research QuestionWhat is the prevalence and clinical significance of Aspergillus-associated conditions in individuals with bronchiectasis? MethodsBronchiectasis patients enrolled into the EMBARC registry from 2015 to 2022 with laboratory testing for Aspergillus lung disease (total IgE, specific IgE to Aspergillus or Aspergillus skin test, IgG to Aspergillus and blood eosinophil counts) were included for analysis. Modified-ISHAM-ABPA working group criteria (2021) were used to define ABPA. Results9953 patients were included. 608 (6.1%) were classified as having ABPA, 570 (5.7%) showed Aspergillus sensitization, 806 (8.1%) had raised Aspergillus-specific IgG without sensitisation, 184 (1.8%) were both sensitised to Aspergillus and had raised Aspergillus-specific IgG and 619 (6.2%) had eosinophilic bronchiectasis (elevated eosinophil counts without evidence of Aspergillus lung disease). The remaining 72.0% had negative Aspergillus serology. Patients with ABPA, Aspergillus sensitization, and raised Aspergillus-specific IgG had more severe disease, with worse lung function and more frequent exacerbations at baseline. During long-term follow-up, patients with raised Aspergillus-specific IgG had higher exacerbation frequency and more severe exacerbations. Aspergillus sensitization associated with increased exacerbations and hospitalisations only in patients not receiving inhaled corticosteroids. InterpretationAspergillus lung disease is common in bronchiectasis. Raised IgG to Aspergillus is associated with significantly worse outcomes while ABPA and Aspergillus sensitization are associated with severe disease and exacerbations with a risk that is attenuated by inhaled corticosteroid use.

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.

Is Obesity a Problem in New Cystic Fibrosis Treatments?

Malnutrition has always been a problem in CF (cystic fibrosis) patients; however, new treatments with CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators have led to weight gain, with some patients at risk of overweight and obesity. Our study aimed to analyze the evolution of BMI (body mass index) after one year of treatment with triple therapy and the factors associated with weight gain in CF patients undergoing treatment with triple therapy with CFTR protein modulators (ETI) (elexacaftor/tezacaftor/ivacaftor). We conducted a prospective, observational, longitudinal, multicenter study in patients diagnosed with cystic fibrosis, aged 18 years or older, with at least one F508del allele and who underwent ETI therapy for at least one year, from 2020 to 2023. One hundred and eight patients from two cystic fibrosis units in Spain, Princess University Hospital of Madrid (74 patients) and Central University Hospital of Asturias (HUCA) (34 patients), were included. Demographic data, anthropometric data, lung function, and exacerbations were collected, comparing the data in the previous year to the start of therapy with the results after one year of treatment. Multivariant models were developed to account for repeated weight and BMI measurements, using a mixed effects model approach and accounting for possible modifying factors Results: One hundred and eight patients were included in the study, 58 men (53.7%) and 50 women (46.3%) with a mean age of 29.5 ± 9.4 years (18-59). Patient weight and BMI were recorded at baseline and at 3-month intervals during the study period. The weight increased from 59.6 kg to 62.6 kg and BMI increased from 21.9 kg/m2 to 23.0 kg/m2 after one year of treatment (p < 0.0001 for both). The proportion of underweight individuals decreased after one year of ETI therapy, from 9.3% to 1.9%, while the proportion of overweight or obese individuals increased from 8.3% to 22.9 % at the same time (p < 0.001). In relation to exacerbations, there is a significant increase in the number of patients who did not have any exacerbations after one year of treatment, which increased from 10.2% to 46.2% (p < 0.001), while the number of patients who had >4 exacerbations decreased significantly, from 40.7% to 1.9% (p < 0.001). FEV1% (forced expiratory volume) increased from 63.9 ± 20.9 to 76.8 ± 21.4 (p < 0.001) and the VR/TLC (residual volume/total lung capacity) value decreased from 45.1 ± 10.9 to 34.9 ± 6.2 (p < 0.001). The proportion with FEV1% > 80% increased from 23.1% before ETI therapy to 49.1% one year after ETI therapy. We performed multivariate mixed models to evaluate the evolution of BMI changes with time, accounting for repeated measures and for possible modifying factors. After the introduction of the triple therapy, patients included in the study had significant weight gain during the 12 months, and when including different covariates in the multivariate mixed model, we found that lower baseline BMI, lower baseline FEV1 and FVC (forced vital capacity), and higher VR/TLC value and higher number of exacerbations were associated with higher BMI changes over the study period. CF patients treated with triple therapy experience significant weight gain, increasing the proportion of overweight patients. CF patients who experienced greater weight gain were those with worse BMI at the start of treatment, as well as patients with worse lung function and a greater number of exacerbations in the year before starting ETI therapy.

Practical Guidelines by the Andalusian Group for Nutrition Reflection and Investigation (GARIN) on Nutritional Management of Patients with Chronic Obstructive Pulmonary Disease: A Review.

Malnutrition is common in chronic obstructive pulmonary disease (COPD) patients and is associated with worse lung function and greater severity. This review by the Andalusian Group for Nutrition Reflection and Investigation (GARIN) addresses the nutritional management of adult COPD patients, focusing on Morphofunctional Nutritional Assessment and intervention in clinical practice. A systematic literature search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, followed by critical appraisal based on Scottish Intercollegiate Guidelines Network (SIGN) guidelines. Recommendations were graded according to the European Society for Clinical Nutrition and Metabolism (ESPEN) system. The results were discussed among GARIN members, with consensus determined using a Likert scale. A total of 24 recommendations were made: 2(A), 6(B), 2(O), and 14(GPP). Consensus exceeded 90% for 17 recommendations and was 75-90% for 7. The care of COPD patients is approached from a nutritional perspective, emphasizing nutritional screening, morphofunctional assessment, and food intake in early disease stages. Nutritional interventions include dietary advice, recommendations on food group intake, and the impact of specialized nutritional treatment, particularly oral nutritional supplements. Other critical aspects, such as physical activity and quality of life, are also analyzed. These recommendations provide practical guidance for managing COPD patients nutritionally in clinical practice.

The Association Between Air Pollution and Lung Function in Sarcoidosis and Implications for Health Disparities

Sarcoidosis is a granulomatous disease with varying courses of disease progression. Environmental exposures are thought to be contributors to disease onset. Exposure to air pollutants such as fine particulate matter (PM2.5) and nitrogen dioxide (NO2) have been identified as contributors to health disparities in lung diseases; little is known about these environmental exposures' associations with disease outcomes in sarcoidosis. Is higher exposure to PM2.5 and NO2 associated with worse lung function in sarcoidosis? We conducted a retrospective, cross-sectional study of individuals with pulmonary sarcoidosis seen from 2005 to 2015. Home addresses at the year of enrollment were geocoded, and exposure to PM2.5 and NO2 was modeled using high-resolution 1km× 1km annual surface exposure data during the year of enrollment. Racial and sex differences in exposure were determined. Multivariable linear regression models were used to examine the associations between PM2.5 and NO2 and the pulmonary function test (PFT) measures FVC, FEV1, and Dlco. Among the 415 individuals in the analysis, Black individuals had significantly higher exposure to PM2.5 and NO2 compared with non-Hispanic White individuals, 12.2 μg/m3 (SD 2.4) vs11 μg/m3 (SD 2.2) and 6.3 ppb (SD 1.9) vs5.0 ppb (SD 2.0), respectively. Every 1 μg/m3 higher exposure to PM2.5 was associated with 1.12%lower Dlco%predicted (95%CI, -1.83 to -0.41; P< .05). Every 1 ppb higher exposure to NO2 was associated with 1.04%lower Dlco%predicted (95%CI, -1.91 to -0.18; P< .05) in fully adjusted models. There were no significant associations between these pollutants and either FVC or FEV1%predicted. Higher exposure to PM2.5 and NO2 was associated with worse Dlco%predicted. Black individuals with sarcoidosis were exposed to higher PM2.5 and NO2 than non-Hispanic White individuals. Air pollution exposure may be a contributor to reported health disparities in sarcoidosis.

Disparities in outcomes by race and ethnicity in the Canadian cystic fibrosis population

BackgroundCystic Fibrosis has historically been described as a disease that affects people of European ancestry. Consequently, much of what we know about CF is based on evidence generated from data collected in white individuals. This may lead to systematic bias in how non-white people with CF are diagnosed and treated. In this study we compared clinical outcomes between the white and non-white people with CF in Canada. MethodsCanadian CF Registry data collected between 2000 and 2019 were used in this population-based cohort study. Demographic characteristics and clinical outcomes of people with CF identified as white and those identified as non-white were compared. Analyses were adjusted for cohort effects but not socioeconomic status. ResultsBetween 2000 and 2019, 5516 people with CF in the Registry were identified as white and 323 were identified as non-white. At diagnosis, the white and non-white groups were similar with respect to sex at birth, age at diagnosis, prevalence of pancreatic insufficiency, and meconium ileus. The non-white group had similar rates of CF-related complications and bacterial infections compared to the white, but worse lung function, worse nutritional status, lower treatment rates, and higher rate of hospitalizations. During the 20-year study period, the non-white group had a 1.85 higher risk of death compared to the white group (HR 95 %CI 1.39; 2.47). InterpretationThere is an urgent need understand why outcomes for Canadians with CF differ between white and non-white individuals, including the role of socioeconomic circumstances.

Associations between respiratory pathogens and lung function in primary ciliary dyskinesia: cross-sectional analysis from the PROVALF-PCD cohort.

Respiratory pathogens are frequently isolated from airway samples in primary ciliary dyskinesia (PCD) patients. Few studies have investigated associations between these pathogens and lung function, with current management based on evidence from cystic fibrosis. We investigated the association between commonly isolated respiratory pathogens and lung function in PCD patients. Using a cross-sectional design, we prospectively collected clinical and concurrent microbiology data from 408 participants with probable or confirmed PCD, aged ≥5 years, from 12 countries. We used Global Lung Function Initiative 2012 references to calculate forced expiratory volume in 1 s (FEV1) z-scores. For 351 patients (86%) with complete data, we assessed the association of the four most frequently isolated pathogens with lung function by fitting multilevel linear models with country as random intercept, adjusted for age at diagnosis, age at lung function, use of antibiotic prophylaxis and body mass index z-scores. Individuals with Pseudomonas aeruginosa growth in culture had significantly lower FEV1 z-scores (β= -0.87, 95% CI -1.40- -0.34), adjusted for presence of Haemophilus influenzae, methicillin-sensitive Staphylococcus aureus and Streptococcus pneumoniae, and for covariates. When stratified by age, associations remained strong for adults but not for children. Results were similar when ciliary defects by transmission electron microscopy were included in the models and when restricting analysis to only confirmed PCD cases. We found that P. aeruginosa was associated with worse lung function in individuals with PCD, particularly adults. These findings suggest that it is prudent to aim for P. aeruginosa eradication in the first instance, and to treat exacerbations promptly in colonised patients.

Eosinophilic Bronchiectasis: Prevalence, Severity, and Associated Features-A Cohort Study.

Background: Bronchiectasis (BE) has been traditionally associated with neutrophilic inflammation, but eosinophilic bronchiectasis (EB) has recently emerged. Data about prevalence, clinical features, and disease severity are lacking. This study aimed to assess the EB prevalence, compare EB with non-EB, evaluate the Type-2 (T2) high endotype in BE (T2-high EB) versus non-T2-high EB, and identify EB predictors. Methods: We conducted a prospective study involving 153 BE patients. The data collected included clinical, radiological, and microbiological findings. BE severity was assessed using the bronchiectasis severity index (BSI), FACED and E-FACED scores, and the bronchiectasis etiology and comorbidity index (BACI). EB was defined as a blood eosinophil count (BEC) ≥ 300 cells/μL, and T2-high EB as BEC ≥ 300 cells/μL with fractional exhaled nitric oxide (FeNO) ≥ 25 ppb. Results: Prevalence was 27% for EB and 20% for T2-high EB. EB patients exhibited poorer lung function and more severe radiologic features, with significantly higher severity scores [BSI, FACED, E-FACED, BACI (p < 0.05)], and a higher median exacerbation rate [4 (2-5) in EB vs. 2 (1-4) in non-EB, p = 0.0002], compared with non-EB patients. T2-high EB patients showed higher severity scores [BSI, FACED, E-FACED (p < 0.05)], as well as worse lung function parameters [FEV1%, FVC%, FEF 25-75% (p < 0.05)] compared with non-T2-high EB patients. In our study, patients with EB exhibited notably worsened lung function and higher BE severity scores compared with their non-EB counterparts, with exacerbations playing a major role in these differences. We found statistically significant positive correlations between BEC and disease severity scores, such as BSI, FACED, and mMRC, as well as an inverse relationship with pulmonary function. The likelihood of EB being present was significantly higher in association with mMRC ≥ 1 (OR = 2.53; 95% CI, 1.26-5.64), exacerbations/year ≥ 1 (OR = 1.27; 95% CI, 1.0-1.63), and chronic PA colonization (OR = 3.9; 95% CI, 1.08-15.8). Conclusions: EB is a distinct endotype. Dyspnea, exacerbations, and PA colonization may be predictive of EB, emphasizing the importance of early detection for improved outcomes. BEC could serve as a useful biomarker of disease severity to consider when diagnosing EB.

Impact of Air Pollutants on Lung Function and Inflammatory Response in Asthma in Shanghai

Objective Air pollution is a leading public health issue. This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai.Methods The study monitored 27 asthma outpatients for a year, collecting data on weather, patient self-management [daily asthma diary, peak expiratory flow (PEF) monitoring, medication usage], spirometry and serum markers. To explore the potential mechanisms of any effects, asthmatic mice induced by ovalbumin (OVA) were exposed to PM2.5.Results Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma. Acute exposure showed a correlation between PEF and levels of ozone (O3) and nitrogen dioxide (NO2). Chronic exposure indicated that interleukin-5 (IL-5) and interleukin-13 (IL-13) levels correlated with PM2.5 and PM10 concentrations. In asthmatic mouse models, exposure to PM2.5 increased cytokine levels and worsened lung function. Additionally, PM2.5 exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways.Conclusion Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation. Specifically, PM2.5 significantly contributes to these adverse effects. Further research is needed to elucidate the mechanisms by which PM2.5 impacts asthma.

Clinical features of pulmonary hypertension in lymphangioleiomyomatosis

Objective: To describe the prevalence of lymphangioleiomyomatosis-pulmonary hypertension (LAM-PH), to explore the clinical features of patients with LAM-PH, and to evaluate the role of pulmonary artery optical coherence tomography (OCT) in the diagnosis of LAM-PH. Methods: Among 234 patients diagnosed with LAM in our center from June 2017 to August 2023, echocardiography was performed in 167 patients, 15 patients with PH indicated by echocardiography were selected as the LAM-PH group. From the remaining 152 patients, 32 patients were randomly selected as the control group. We compared the demographic data, clinical manifestations, pulmonary function, blood gas analysis, and serum vascular endothelial growth factor D (VEGF-D) levels between the two groups. We also evaluated the data from right heart catheterization in five patients and the images from optical coherence tomography of pulmonary arteries in two patients. Results: Echocardiography showed pulmonary hypertension in 15 patients (8.98%). Compared with the control group, LAM-PH group had a higher proportion of patients receiving oxygen therapy. Patients with PH had lower FEV1, FVC, FEV1/FVC, DLCO and higher serum VEGF-D levels compared with those without PH. Right heart catheterization was performed in five patients. Five patients had a pre-capillary pattern and three of these patients had severe pulmonary hypertension. Optical coherence tomography showed that there were no obvious abnormalities in the intima and lumen of the blood vessels in the two patients. Conclusions: The prevalence of PH in LAM is low. Patients in the LAM-PH group had more severe hypoxemia, worse lung function and higher serum VEGF-D levels than those in the control group. PH in LAM is mainly pre-capillary. Optical coherence tomography can evaluate the pulmonary artery vascular condition and help to identify the cause of pulmonary hypertension in LAM patients.

The foregut in cystic fibrosis.

The aerodigestive organs share a kindred embryologic origin that allows for a more complete explanation as to how the foregut can remain a barrier to normalcy in people with cystic fibrosis (pwCF). The structures of the aerodigestive tract include the nasopharynx, the oropharynx, the hypopharynx, the esophagus, the stomach, as well as the supraglottic, glottic, and subglottic tubular airways (including the trachea). Additional gastrointestinal (GI) luminal/alimentary organs of the foregut include the duodenum. Extraluminal foregut structures include the liver, the gall bladder, the biliary tree, and the pancreas. There are a variety of neurologic controls within these complicated anatomic compartments to separate the transit of food and liquid from air. These structures share the same origin from the primitive foregut/mesenchyme. The vagus nerve is a critical structure that unites respiratory and digestive functions. This article comments on the interconnected nature of cystic fibrosis and the GI tract. As it relates to the foregut, this has been typically treated as simple "reflux" as the cause of worsened lung function in pwCF. That terms like gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD), heartburn, and regurgitation are used interchangeably to reflect pathology further complicates matters; we offer a more physiologically accurate term called "GI-related aspiration" or "GRASP." Broadly, this term reflects that aspiration of foregut contents from the duodenum through the stomachto the esophagus, into the pharynx and the respiratory tree in pwCF. As a barrier to normalcy in pwCF, GRASP is fundamentally two disease processes-GERD and gastroparesis-that likely contribute most to the deterioration of lung disease in pwCF. In the modulator era, successful GRASP management will be critical, particularly in those post-lung transplantation (LTx), only through successful management of both GERD and gastroparesis. Standardization of clinical management algorithms for GRASP in CF-related GRASP is a key clinical and research gap preventing normalcy in pwCF; what exists nearly exclusively addresses surgical evaluations or offers guidance for the management of GI symptoms alone (with unclear parameters for respiratory disease considerations). We begin first by describing the result of GRASP damage to the lung in various stages of lung disease. This is followed by a discussion of the mechanisms by which the digestive tract can injure the lungs. We summarize what we anticipate future research directions will be to reduce the impact of GRASP as a barrier to normalcy in pwCF.

Pattern of occupational lung disease among industrial workers attending a medical college of Eastern India.

Occupational lung diseases (OLDs) contribute a significant proportion to the global burden of pulmonary morbidities but are grossly misdiagnosed due to the relative lack of attribution given to occupational exposures. Obstructive lung diseases are known to be associated with long-lasting disability and loss of earning capacity (LOEC) among workers in industrial setups, thus reducing nationwide productivity. In this context, the study aimed to find out the pattern of OLD and factors associated with the severity of it among patients in a tertiary care hospital. The study was a record-based secondary data analysis conducted in the Medical Records Department of a Medical College in Kolkata. A computerized database of patients attending Special Medical Board (SMB) examinations from the Department of Medical Records was utilized for data collection. A data abstraction format was constructed to collect information on pulmonary morbidity, occupational exposure, and sociodemographic and behavioral variables. Extracted data were analyzed in Microsoft Excel and Statistical Package for Social Sciences (SPSS) software. After a review of records, it was shown that 62.3% (66 out of 106 people) of the study subjects had an obstructive type of OLD, the most common being Jute Byssinosis. A negative correlation (Spearman's ρ = -0.136) was found between pulmonary function (FEV1/FVC) and LOEC (%) in the study subjects. In the multivariable logistic regression, exposure to organic dust was found to be significantly associated with worsened lung function {adjusted-Odd's Ratio (95% Confidence Interval) =3.11 (1.1-8.8), P value = 0.03}. OLD is an understated health issue, especially in an industrial diaspora of developing countries, like India. Healthcare facilities should utilize their resources properly for the advancement of medical surveillance in industries where organic dust is produced. Health education of the stakeholders regarding the consequences of OLDs and the benefits of preventive primary approaches will go a long way in alleviating the burden of disease.

YAP1 inhibits the senescence of alveolar epithelial cells by targeting Prdx3 to alleviate pulmonary fibrosis

The senescence of alveolar type II (AT2) cells impedes self-repair of the lung epithelium and contributes to lung injury in the setting of idiopathic pulmonary fibrosis (IPF). Yes-associated protein 1 (YAP1) is essential for cell growth and organ development; however, the role of YAP1 in AT2 cells during pulmonary fibrosis is still unclear. YAP1 expression was found to be downregulated in the AT2 cells of PF patients. Deletion of YAP1 in AT2 cells resulted in lung injury, exacerbated extracellular matrix (ECM) deposition, and worsened lung function. In contrast, overexpression of YAP1 in AT2 cells promoted alveolar regeneration, mitigated pulmonary fibrosis, and improved lung function. In addition, overexpression of YAP1 alleviated bleomycin (BLM) -induced senescence of alveolar epithelial cells both in vivo and in vitro. Moreover, YAP1 promoted the expression of peroxiredoxin 3 (Prdx3) by directly interacting with TEAD1. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in BLM-treated MLE-12 cells, whereas depletion of Prdx3 partially abrogated the protective effect of YAP1. Furthermore, overexpression of Prdx3 facilitated self-repair of the injured lung and reduced ECM deposition, while silencing Prdx3 attenuated the antifibrotic effect of YAP1. In conclusion, this study demonstrated that YAP1 alleviates lung injury and pulmonary fibrosis by regulating Prdx3 expression to improve mitochondrial dysfunction and block senescence in AT2 cells, revealing a potential novel therapeutic strategy for pulmonary fibrosis.

BMAL1 sex-specific effects in the neonatal mouse airway exposed to moderate hyperoxia.

Supplemental O2 (hyperoxia) is a critical intervention for premature infants (<34 weeks) but consequently is associated with development of bronchial airway hyperreactivity (AHR) and asthma. Clinical practice shifted toward the use of moderate hyperoxia (<60% O2), but risk for subsequent airway disease remains. In mouse models of moderate hyperoxia, neonatal mice have increased AHR with effects on airway smooth muscle (ASM), a cell type involved in airway tone, bronchodilation, and remodeling. Understanding mechanisms by which moderate O2 during the perinatal period initiates sustained airway changes is critical to drive therapeutic advancements toward treating airway diseases. We propose that cellular clock factor BMAL1 is functionally important in developing mouse airways. In adult mice, cellular clocks target pathways highly relevant to asthma pathophysiology and Bmal1 deletion increases inflammatory response, worsens lung function, and impacts survival outcomes. Our understanding of BMAL1 in the developing lung is limited, but our previous findings show functional relevance of clocks in human fetal ASM exposed to O2. Here, we characterize Bmal1 in our established mouse neonatal hyperoxia model. Our data show that Bmal1 KO deleteriously impacts the developing lung in the context of O2 and these data highlight the importance of neonatal sex in understanding airway disease.

A Secondary Analysis of Gender Respiratory Features for Ultrasonography Bilateral Diaphragm Thickness, Respiratory Pressures, and Pulmonary Function in Low Back Pain.

The aim of the present study was to determine the gender respiratory differences of bilateral diaphragm thickness, respiratory pressures, and pulmonary function in patients with low back pain (LBP). A sample of 90 participants with nonspecific LBP was recruited and matched paired by sex (45 women and 45 men). Respiratory outcomes included bilateral diaphragm thickness by ultrasonography, respiratory muscle strength by maximum inspiratory (MIP) and expiratory (MEP) pressures, and pulmonary function by forced expiratory volume during 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC spirometry parameters. The comparison of respiratory outcomes presented significant differences (p < 0.001), with a large effect size (d = 1.26-1.58) showing means differences (95% CI) for MIP of -32.26 (-42.99, -21.53) cm H2O, MEP of -50.66 (-64.08, -37.25) cm H2O, FEV1 of -0.92 (-1.18, -0.65) L, and FVC of -1.00 (-1.32, -0.69) L, with lower values for females versus males. Gender-based respiratory differences were presented for maximum respiratory pressures and pulmonary function in patients with nonspecific LBP. Women presented greater inspiratory and expiratory muscle weakness as well as worse lung function, although these differences were not linked to diaphragm thickness during normal breathing.

Prospective association between social isolation, loneliness and lung function among Chinese middle-aged and older adults.

Previous research has highlighted a heightened occurrence of social isolation and loneliness in older adults diagnosed with chronic lung diseases. Nevertheless, there exists a dearth of studies that have explored the influence of impoverished social relationships on lung function. This study aimed to examine the longitudinal association between social isolation, loneliness and lung function over 4 years among middle-aged and older Chinese adults. This study employed two waves (2011 and 2015) of data from the China Health and Retirement Longitudinal Study (CHARLS). The analysis was limited to participants aged 45 years and above and stratified based on gender (3325 men and 3794 women). The measurement of peak expiratory flow (PEF) served as an indicator for assessing lung function. Lagged dependent variable regression models, accounting for covariates, were employed to explore the relationship between baseline social isolation and loneliness and the subsequent PEF. For women, social isolation was significantly associated with the decline in PEF at follow-up (β = -.06, p < .001) even after adjusting for all covariates; no significant correlation was observed between loneliness and PEF. Among men, there was no significant association found between either social isolation or loneliness and PEF. Social isolation is prospectively associated with worse lung function in middle-aged and older Chinese women but not men. The results highlight the importance of promoting social relationships in public health initiatives, especially in groups that are more vulnerable.

The correlation between smoking cumulative dose based on Brinkman Index with peak expiratory flow rate.

Indonesia is the country with the highest prevalence of smokers above 15 years old according to WHO, with a percentage of 76.2%. Smoking-induced lung damage is characterized by inflammation, leading to the destruction of lung parenchyma and airway obstruction, ultimately worsening lung function parameters. This study aims to find correlation between cumulative dose of smoking based on Brinkman index (BI) with Peak Expiratory Flow Rate (PEFR). This is a cross-sectional correlative study conducted on January-March 2020. Data were collected through history taking and PEFR measured with a peak flowmeter by taking the average of three peak flowmeter measurements, each separated by a 2-min interval. Inclusion criteria include male active smokers, aged 30 to 40 years, who have had a smoking history for at least 1 year. Exclusion criteria are as follows: uses e-cigarretes for smoking, has a history of chronic lung diseases such as tuberculosis, pneumonia, post-COVID-19 syndrome, asthma, and has not smoked in the last 28 days. A total of 48 male smokers are included in this study. The mean age of participants was 35.91 years, with a history of smoking of 18.12 years, and 12.5 cigarettes smoked daily. Patients included in this study had BI classified as mild (47.91%), moderate (47.91%), and severe (4.16%). PEFR in patients was classified into green (10.41%), yellow (83.33%), and red (6.25%). Analysis showed significant negative correlation between BI and PEFR (r = -0.721; p < 0.001) suggesting that increasing Brinkman Index may lead to a decrease in PEFR. Higher BI correlates with a decrease in PEFR. PEFR may prove to be useful in early detection of reduced pulmonary function. Further trials conducted on larger sample sizes and evaluating other lung function parameters are recommended.

Role of transient receptor potential ankyrin 1 in idiopathic pulmonary fibrosis: modulation of M2 macrophage polarization

Idiopathic pulmonary fibrosis (IPF) poses significant challenges due to limited treatment options despite its complex pathogenesis involving cellular and molecular mechanisms. This study investigated the role of transient receptor potential ankyrin 1 (TRPA1) channels in regulating M2 macrophage polarization in IPF progression, potentially offering novel therapeutic targets. Using a bleomycin-induced pulmonary fibrosis model in C57BL/6J mice, we assessed the therapeutic potential of the TRPA1 inhibitor HC-030031. TRPA1 upregulation was observed in fibrotic lungs, correlating with worsened lung function and reduced survival. TRPA1 inhibition mitigated fibrosis severity, evidenced by decreased collagen deposition and restored lung tissue stiffness. Furthermore, TRPA1 blockade reversed aberrant M2 macrophage polarization induced by bleomycin, associated with reduced Smad2 phosphorylation in the TGF-β1-Smad2 pathway. In vitro studies with THP-1 cells treated with bleomycin and HC-030031 corroborated these findings, highlighting TRPA1's involvement in fibrotic modulation and macrophage polarization control. Overall, targeting TRPA1 channels presents promising therapeutic potential in managing pulmonary fibrosis by reducing pro-fibrotic marker expression, inhibiting M2 macrophage polarization, and diminishing collagen deposition. This study sheds light on a novel avenue for therapeutic intervention in IPF, addressing a critical need in the management of this challenging disease.Graphical abstract

Longitudinal changes in lung function following post-9/11 military deployment in symptomatic veterans

RationaleExposure to burn pit smoke, desert and combat dust, and diesel exhaust during military deployment to Southwest Asia and Afghanistan (SWA) can cause deployment-related respiratory diseases (DRRDs) and may confer risk for worsening lung function after return. MethodsStudy subjects were SWA-deployed veterans who underwent occupational lung disease evaluation (n = 219). We assessed differences in lung function by deployment exposures and DRRD diagnoses. We used linear mixed models to assess changes in lung function over time. ResultsMost symptomatic veterans reported high intensity deployment exposure to diesel exhaust and burn pit particulates but had normal post-deployment spirometry. The most common DRRDs were deployment-related distal lung disease involving small airways (DDLD, 41%), deployment-related asthma (DRA, 13%), or both DRA/DDLD (24%). Those with both DDLD/DRA had the lowest estimated mean spirometry measurements five years following first deployment. Among those with DDLD alone, spirometry measurements declined annually, adjusting for age, sex, height, weight, family history of lung disease, and smoking. In this group, the forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) ratio declined 0.2% per year. Those with more intense inhalational exposure had more abnormal lung function. We found significantly lower estimated FVC and total lung capacity five years following deployment among active duty participants (n = 173) compared to those in the reserves (n = 26). ConclusionsMore intense inhalational exposures were linked with lower post-deployment lung function. Those with distal lung disease (DDLD) experienced significant longitudinal decline in FEV1/FVC ratio, but other DRRD diagnosis groups did not.

Do Causes Influence Functional Aspects and Quality of Life in Patients with Nonfibrocystic Bronchiectasis?

The denomination of noncystic fibrosis bronchiectasis (NCFB) includes several causes, and differences may be expected between the patient subgroups regarding age, comorbidities, and clinical and functional evolution. This study sought to identify the main causes of NCFB in a cohort of stable adult patients and to investigate whether such conditions would be different in their clinical, functional, and quality of life aspects. Between 2017 and 2019, all active patients with NCFB were prospectively evaluated searching for clinical data, past medical history, dyspnea severity grading, quality of life data, microbiological profile, and lung function (spirometry and six-minute walk test). There was a female predominance; mean age was 54.7 years. Causes were identified in 82% of the patients, the most frequent being postinfections (n = 39), ciliary dyskinesia (CD) (n = 32), and chronic obstructive pulmonary disease (COPD) (n = 29). COPD patients were older, more often smokers (or former smokers) and with more comorbidities; they also had worse lung function (spirometry and oxygenation) and showed worse performance in the six-minute walk test (6MWT) (walked distance and exercise-induced hypoxemia). Considering the degree of dyspnea, in the more symptomatic group, patients had higher scores in the three domains and total score in SGRQ, besides having more exacerbations and more patients in home oxygen therapy. Causes most identified were postinfections, CD, and COPD. Patients with COPD are older and have worse pulmonary function and more comorbidities. The most symptomatic patients are clinically and functionally more severe, besides having worse quality of life.