Reduced Lung Function Research Articles

Reduced lung function and health-related quality of life after treatment for pulmonary tuberculosis in Gambian children: a cross-sectional comparative study

BackgroundPost-tuberculosis (post-TB) lung disease is an under-recognised consequence of pulmonary tuberculosis (pTB). We aimed to estimate the prevalence of residual lung function impairment and reduced health-related quality of life (HRQoL)...

Assessment of Respiratory Morbidity and Epidemiological Survey of Tobacco Smokers and Non-Smokers Among Educated Young Adults in Visva-Bharati, Santiniketan: A Case Study

Tobacco smoking among adults have become a serious health concern worldwide due to its increasing addicting nature. Tobacco smoke contains highly harmful gaseous and volatile chemical substances that impair the respiratory system and reduce lung function capacity. The study's primary objectives were to investigate the cause of smoking, behaviour of smokers, social responsibility, family history of the smoker, and significant respiratory health problems among young educated adults. The survey was conducted with some pre-framed questionnaires and screening relevant to the subjects for our study. The respiratory health assessment was carried out by questionnaire-based personal interviews for different respiratory and non-respiratory health symptoms. Subsequently, the lung function or pulmonary function test (LFT or PFT) for selected individuals was performed, revealing the lung performances of smokers and non-smokers. The LFT or PFT test predicts the normal and abnormal breathing patterns of exposed and non-exposed studied groups. The significant findings indicated that curiosity (72%) and displaying of smartness were the leading cause of smoking in early adulthood (16 to 20 years). Family history of smoking also influenced young adults to initiate regular smoking. Smoking within thirty minutes after waking up in the morning was - a habit in 52% of smokers. Findings revealed that 50% of the heavy smokers smoke 11-15 units daily. The average weekly expenditure for the smoking materials was INR 100 to 150 (26.32%) rupees for smokers. Spirometric indices such as forced vital capacity (FVC), forced expiratory volume in one second (FEV1), percentage forced expiratory volume in one second (FEV1%), and peak expiratory flow rate (PEFR), showed a reduced performance of lungs in smokers as compared to their fellow non-smokers. This study has focused on the smoking behaviour of educated young adults and revealed the presence of different respiratory symptoms in smokers than non-smokers, which is an immerging health issue. The study revealed that smokers grouped are more susceptible to lung diseases than non-smokers in the future due to their reduced lung function capacity compared to non-smokers.

Association of lung function with the risk of cardiovascular diseases and all-cause mortality in patients with diabetes: Results from NHANES III 1988-1994.

ObjectiveThe potential effects of pulmonary dysfunction on cardiovascular diseases (CVD) and all-cause mortality are receiving attention. The current study aimed to explore whether reduced lung function predicts CVD and all-cause mortality in people with diabetes.MethodsA total of 1,723 adults with diabetes (mean age 60.2 years) were included in the National Health and Nutrition Examination Survey (NHANES III). Death outcomes were ascertained by linkage to the database records through 31 December 2015. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coronary heart disease (CHD), CVD, and all-cause mortalities. We conducted stratified analyses based on age, body mass index (BMI), history of hypertension, and dyslipidemia.ResultsDuring a mean follow-up of 14.62 years (25,184 person-year), a total of 1,221 deaths were documented, of which 327 were CHD, 406 were CVD, and 197 were cancer. After multi-factor adjustment, participants with lower FEV1 and FVC had a higher risk of CHD, CVD, and all-cause mortality. This association was also found in lower FVC and a higher risk of cancer mortality [HR: 3.85 (1.31–11.32); P for trend = 0.040], but the association of FEV1 was attenuated after adjustment for covariates [HR:2.23 (0.54–9.17); P for trend = 0.247]. In subgroup analysis, we found that the adverse associations of FEV1 and FVC with CVD mortality were observed in subgroups of age, BMI, and history of hypertension and dyslipidemia.ConclusionDeclined lung function was associated with a higher risk of CVD and all-cause mortality in people with diabetes. Lung function tests, especially FEV1 and FVC, should be encouraged to provide prognostic and predictive information for the management of CVD and all-cause mortality in patients with diabetes.

The relationship of early-life household air pollution with childhood asthma and lung function.

The increase in childhood asthma over the past few decades has made it an important public health issue. Poor lung function growth associated with some phenotypes of asthma compounds its long-term impact on the individual. Exposure to early-life household risk factors is believed to be linked with respiratory health while infants' lungs are still developing. This review summarises epidemiological studies and mechanistic evidence focusing on the detrimental effects of early-life household air exposures on the respiratory health of children, in particular effects on asthma and lung function. Many early-life household air exposures, including tobacco smoke, gases from heating and cooking, mould/dampness and cleaning products are associated with childhood asthma development and lung function growth. These exposures may alter structural and mechanical characteristics of infants' lungs and contribute to deficits in later life. In addition, some risk factors, including tobacco smoke and cleaning products, can transmit effects across generations to increase the risk of asthma in subsequent generations. This review supports the hypothesis that risks of asthma and accelerated lung ageing are established in early life. The timing of exposure may be critical in the pathogenesis of respiratory diseases, in terms of future risk of asthma and reduced lung function in adults.

Lung function reduction among welders

Welding is associated with regular exposure to dust and fumes. Many studies have proven that there is a decrease in lung function due to exposure to this agent. This study aimed to quantitatively analyze the risk factors of impaired lung function among welders in Binong, Tangerang, Indonesia. This was a cross-sectional study design. The lung function of 30 welders is measured by spirometry using the parameters of vital capacity (VC), forced vital capacity (FCV), forced expiratory volume in one second (FEV1), and the ratio of FEV1/FVC. Chi-square analysis was performed and showed that 20 respondents (67%) had impaired lung function, while 10 respondents (33%) had normal lung function. Another factor contributing to impaired lung function among welding workers was their nutritional status, whereby respondents with abnormal nutritional status (body mass index (BMI) 18.4 or ≥25.1) were at 2.15 times higher risk of suffering from impaired lung function compared to respondents with normal nutritional status. Additionally, respondents who did not exercise regularly were at 1.22 times higher risk of impaired lung function compared to those who exercised regularly. Therefore, it is necessary to collaborate with the local community health center to monitor the health of the welders. It is recommended to carry out regular health checks, specifically pulmonary examination, at least once at a year to keep track of the health development of the workers. It is important to equip the workspace with a good ventilation system, and to have the welder work with appropriate personal protective equipment.

Do Childhood Cancer Survivors Have Reduced Lung Function Compared To Healthy Individuals?

PURPOSE: to evaluate lung function in childhood cancer survivors (CCS) compared to age and sex-matched controls in Norway and Switzerland. METHODS: In this multicenter European cross-sectional study (Oslo, Bergen, Basel), 157 CCS and 113 controls (age range 9-18 years) performed spirometry and whole-body plethysmography, and measured lung diffusion capacity and blood haemoglobin levels, according to guidelines. Forced expiratory volume in one sec (FEV1), forced vital capacity (FVC), total lung capacity (TLC), transfer coefficient (KCO) and total lung diffusion capacity for carbon monoxide (DLCO) were recorded. Predicted values were according to Global Lung Initiative. RESULTS: Mean age (standard deviation) of all participants was 13.4 (2.6) years. The most common cancer diagnoses were leukemia (50%), brain tumors (11%) and lymphoma (10%). The majority (77%) of CCS had received chemotherapy with anthracyclines. Tabulated preliminary data showing differences between CCS and controls: CONCLUSIONS: Lung function was well preserved in CCS despite significant differences between CCS and controls. There was no evidence of diffusion limitation induced by treatment toxicity.

Novel Lung Growth Strategy with Biological Therapy Targeting Airway Remodeling in Childhood Bronchial Asthma.

Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma.

Data from the Russian Severe Asthma Registry (RSAR)

Creation of the "Russian register of patients with severe asthma" and obtaining data on the population characteristics of patients with severe asthma (SA), the prevalence of SA phenotypes, treatment outcomes and the degree of disease control. Observational non-interventional study, which consists in the data analysis obtained on the basis of registration cards of the Russian Register of Patients with Severe Bronchial Asthma, data collection in which was carried out on the Oracle XE platform. Statistical data processing was carried out using Power BI, PSPP and Microsoft Excel spreadsheets. The study included 4376 adult patients (mean age 60.613.5 years, 65% women) diagnosed with SA from 57 regions of Russia for the period from June 2018 to December 2021. T2 inflammation was detected in 94.8% of patients when determining blood eosinophils and IgE of blood serum; 69% of patients with SA corresponded to the allergic phenotype. 83.3% of patients had no control of BA and 53% had 1 or more exacerbations of BA per year. 8% of patients received systemic corticosteroids as a permanent therapy, while biologics 10.6%. The vast majority of adult patients with SA correspond to the T2 phenotype, have uncontrolled asthma with a high frequency of exacerbations and reduced lung function. A more favorable course of the disease was noted in patients receiving biological therapy, which requires appropriate measures to increase the possibility of access to this type of therapy.

Biologic therapies for asthma in underserved populations

Black and Hispanic children living in disadvantaged urban environments in the USA face a disproportionate burden of asthma, experiencing the highest rates of morbidity and mortality in the country. 1 Altman MC Calatroni A Ramratnam S et al. Endotype of allergic asthma with airway obstruction in urban children. J Allergy Clin Immunol. 2021; 148: 1198-1209 Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar The repeated exacerbations that accompany severe eosinophilic asthma in these populations can lead to loss of lung function, increased asthma severity, and progression to a pattern of fixed obstructive lung disease by early adulthood. 2 O'Brian AL Lemanske Jr, RF Evans MD Gangnon RE Gern JE Jackson DJ Recurrent severe exacerbations in early life and reduced lung function at school age. J Allergy Clin Immunol. 2012; 129: 1162-1164 Summary Full Text Full Text PDF PubMed Scopus (27) Google Scholar , 3 McGeachie MJ Yates KP Zhou X et al. Patterns of growth and decline in lung function in persistent childhood asthma. N Engl J Med. 2016; 374: 1842-1852 Crossref PubMed Scopus (350) Google Scholar Worryingly, in a substantial proportion of these children, conventional guideline-directed therapies, such as corticosteroids and long-acting β agonists, do not improve asthma control. Consequently, the identification of novel therapeutic strategies represents an important unmet need for underserved Black and Hispanic children living in urban areas. 4 Gonzalez Burchard E Borrell LN Need for racial and ethnic diversity in asthma precision medicine. N Engl J Med. 2021; 385: 2297-2298 Crossref PubMed Scopus (5) Google Scholar Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trialPhenotype-directed therapy with mepolizumab in urban children with exacerbation-prone eosinophilic asthma reduced the number of exacerbations. Full-Text PDF

Protocol for the Vitamin D Oral Replacement in Asthma (VDORA) study

Obesity and asthma are epidemic in the United States and obesity is an independent risk factor for asthma. Low vitamin D levels (i.e. serum 25-hydroxyvitamin D) have been reported in patients with reduced lung function, more frequent respiratory infections, and asthma exacerbations. Experts have proposed that serum levels > 40 ng/mL are required to offer the immunomodulatory benefits of vitamin D. Low vitamin D levels are common in both obesity and asthma, but it is not known whether supplementation with vitamin D improves asthma symptoms. Guidance for drug development stresses the importance of early phase studies to establish accurate population pharmacokinetics (PK) and drug dosing prior to larger phase 3 trials. The PK of this fat-soluble vitamin in children with increased adiposity are unknown; as are the doses need to reach proposed immunomodulatory levels. The objective of this study is to characterize the PK of vitamin D in children with obesity. Children ages 6‐–18 years who had physician diagnosed asthma and a body mass index (BMI) >85th percentile will be randomized to receive either standard daily dosing or loading doses followed by standard daily dosing. Blood samples will be obtained to characterize the PK of vitamin D. The results of this study will be used to identify a sufficient dose of vitamin D supplement to raise serum levels above a pre-specified value that may result in anti-inflammatory actions that could improve asthma symptoms.

HIMA2: high-dimensional mediation analysis and its application in epigenome-wide DNA methylation data

Mediation analysis plays a major role in identifying significant mediators in the pathway between environmental exposures and health outcomes. With advanced data collection technology for large-scale studies, there has been growing research interest in developing methodology for high-dimensional mediation analysis. In this paper we present HIMA2, an extension of the HIMA method (Zhang in Bioinformatics 32:3150–3154, 2016). First, the proposed HIMA2 reduces the dimension of mediators to a manageable level based on the sure independence screening (SIS) method (Fan in J R Stat Soc Ser B 70:849–911, 2008). Second, a de-biased Lasso procedure is implemented for estimating regression parameters. Third, we use a multiple-testing procedure to accurately control the false discovery rate (FDR) when testing high-dimensional mediation hypotheses. We demonstrate its practical performance using Monte Carlo simulation studies and apply our method to identify DNA methylation markers which mediate the pathway from smoking to reduced lung function in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Lung transplantation and concomitant cardiac surgical procedures: A systematic review and meta-analysis.

Lung transplantation is an effective treatment option for end-stage lung diseases. In some cases, these patients may also have underlying cardiac disease which may require surgical intervention before or during transplantation. Concomitant cardiac surgery may often be preferred, as reduced lung function precludes these patients from pre-transplant surgery. Our meta-analysis sought to examine the impact of lung transplantation paired with concomitant cardiac surgery on long-term mortality. We conducted a systematic review of the MEDLINE, Embase, and Cochrane databases. Our primary outcome was overall mortality. Secondary outcomes included length of stay (LOS) in hospital and serious postoperative complication rates. We used a meta-analytic model to determine the differences in the above outcomes between patients who underwent lung transplantation with or without concomitant cardiac surgery. Out of the 1876 articles screened, 7 met our pre-determined inclusion criteria. Lung transplantation with concomitant cardiac surgery was not associated with increased mortality compared to lung transplantation alone (hazard ratio = 1.02; 95% confidence interval [CI] = 0.80-1.31; I2 = 0%; p = .99). LOS in hospital was not significantly different between groups (standardized mean difference = 0.32; 95% CI = -0.91 to 1.55). Postoperative complication rates were also reported but not analyzed due to missing data. There was no significant difference in mortality rates in patients undergoing lung transplantation with or without concomitant cardiac surgery at 1, 3, and 5 years. However, postoperative complication rates were higher in the concomitant group. The decision to perform concomitant procedures should be tailored to each patient's clinical condition.

Short-term effects of the toxic component of traffic-related air pollution (TRAP) on lung function in healthy adults using a powered air purifying respirator (PAPR)

Short-term exposure to traffic-related air pollution (TRAP) are associated with reduced lung function. However, TRAP is a mixture of various gaseous pollutants and particulate matter (PM), and therefore it is unknown that which components of TRAP are responsible for the respiratory toxicity. Using a powered air-purifying respirator (PAPR), we conducted a randomized, double-blind, crossover trial in which 40 adults were exposed to TRAP for 2 h at the sidewalk of a busy road. During the exposure, the participants wore the PAPR fitted with a PM filter, a PM and volatile organic compounds (VOCs) filter, or a sham filter (no filtration, Sham mode). The participants were blinded to the type of filter in their PAPR, and experienced three exposures, once for each intervention mode in random order. We measured two lung function measures (forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC]) and an airway inflammation marker (fraction of exhaled nitric oxide [FENO]) before and immediately after each exposure, and further measured them at different time periods after exposure. We applied linear mixed effect models to estimate the effects of the interventions on the changes of lung function from baseline values after controlling for other covariates. Compared to baseline, exposing to TRAP decreased FEV1 and FVC, and increased FEV1/FVC and FENO in all three intervention modes. The mixed models showed that with the sham mode as reference, lung function and airway inflammation post exposure were significantly improved by filtering both PM and VOCs, but marginally affected by filtering only PM. In conclusion, the VOCs component of TRAP is responsible for the reduction in lung function caused by short-term exposure to TRAP. However, the result needs to be interpreted cautiously before further verified by laboratory experiment using purely isolated component(s) of TRAP.

Risk of Pulmonary-Reproductive Dysfunctions, Inflammation and Oxidative DNA Damage in Exposure to Polycyclic Aromatic Hydrocarbon in Cigarette Smokers.

Background: Exposure to cigarette smoke has been associated with pulmonary and reproductive dysfunctions; inflammatory response, oxidative stress and oxidative DNA damage induced by polycyclic aromatic hydrocarbons (PAHs) present in cigarette smoke have been implicated in the pathogenesis of these disorders. The peak expiratory flow rate (PEFR), a biomarker of inflammation and oxidative DNA damage (8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor alpha (TNF-α)), reproductive hormones (testosterone (TST), luteinizing hormone (LH), follicle stimulating hormone (FSH)) cotinine and urinary PAH metabolite (1-hydroxypyrene (1-HOP)) were estimated in male active smokers. Methods: One hundred men aged 20-47 years, comprising 50 active male smokers and 50 non-smokers, were randomly recruited into this comparative cross-sectional study. The PEFR was measured using a peak flow meter, serum levels of cotinine, FSH, LH, TST, TNF-α, and urine 8-OHdG by enzyme-linked immunosorbent assay and 1-HOP by high-performance liquid chromatography. Data analysis was done using a t-test and correlation analysis at p≤0.05. Results: Smokers had significantly higher cotinine (49.73±31.76 versus 0.51±0.69 ng/ml, p≤0.001), 8-OHdG (16.34±12.10 versus 5.79±2.14 ng/ml, p≤0.001) and lower PEFR (309.20±56.05 versus 452.80±45.76 L/min, p≤0.001) and LH (5.75±2.06 versus 6.97±2.79 mIU/ml, p=0.015) compared to non-smokers. Duration of exposure to cigarette smoke correlated positively with cotinine (r=0.937, p≤0.001) and 1-HOP (r=0.813, p≤0.001) while cotinine correlated positively with 1-HOP (r=0.863, p≤0.001) only in smokers. Conclusion: Reduced lung function and luteinizing hormone and concurrent increase in oxidative DNA damage associated with exposure to cigarette smoke may suggest the involvement of PAH-induced DNA damage in the development of pulmonary and reproductive impairment in smokers.

Press tack needle stimulation for blunt chest trauma: a randomized double-blind control trial.

OBJECTIVESBlunt chest trauma is often associated with severe pain, reduced lung function and decreased sleep quality. This study aims to investigate the immediate and long-term effect of acupuncture on these factors using a randomized control double-blind design.METHODSA total of 72 patients were randomized into 2 groups: treatment group (press tack acupuncture) and control group (press tack placebo). The face rating scale, numerical rating scale (NRS), portable incentive spirometer and Verran Snyder-Halpern sleep scale were measured at baseline, immediately after the intervention, and at the 4th day, with 2-weeks and 3-months follow-ups.RESULTSThere were no significant changes between the groups at the baseline measurements, with the exception of hypertension comorbidity. Immediately after the intervention and on the 4th day follow-up, the patients in the treatment group showed a significantly lower face rating scale when compared to the control (P < 0.05). There were no significant changes in any of the other measurements between the groups (P > 0.05). Subgroup analysis revealed that the NRS for turn over on the 4th day was reduced significantly in the treatment group of patients without lung contusion (P < 0.05). For patients without pleural drainage, cough NRS in the treatment group was significantly reduced in the 2-week follow-up (P < 0.05).CONCLUSIONSThis study showed that press tack acupuncture effects on pain reduction were inconclusive. However, future studies on the effect of acupuncture on blunt chest trauma patients are needed.Clinical trial registrationclinicaltirl.gov: NCT04318496.

HEALTH-RELATED QUALITY OF LIFE, LUNG FUNCTION AND ASTHMA CONTROL IN OBESE ASTHMATIC INDIAN CHILDREN

Objective: Obesity is a major risk factor for asthma in children. Obese children have an increased risk of asthma; have more frequent and severe exacerbations, decreased lung function, and poor quality of life. However, the relationship between obesity, lung function, and asthma control remains unclear in obese asthmatic Indian children. Therefore, we examined the relationship of body mass index (BMI) with lung function, asthma control, and quality of life in obese asthmatic children. Design and method: Forty-seven children (8–15 years) with asthma according to Global Initiative for Asthma (GINA) guidelines were enrolled in the study from the Pediatric Chest Clinic of All India Institute of Medical Sciences, New Delhi, India. Weight was recorded to the nearest 0.1 kg and height was measured using a stadiometer nearest to 0.1 cm. The measurements of height and weight were used to calculate BMI. BMI derived was categorized by using Z score tables of WHO-BMI for age standards for boys and girls between 5 and 19 years. Lung function was assessed using spirometry parameters (Super spiro MK2 Micro Medical Ltd, UK), HRQoL was assessed using Juniper’s Pediatric Asthma Quality of Life Questionnaire (PAQLQ), and level of asthma control was assessed by Juniper’s Asthma control questionnaire (ACQ). ACQ score ranges from 0 (well controlled) to 6 (extremely poorly controlled). Spearman’s rank correlation analysis was performed to study the relationship between BMI, lung function parameters, PAQLQ score, and asthma control score Results: Obese children had mean (SD) age of 10.7 (2.5) years, BMI = 25.9 ± 7.5 kg/m2, forced expiratory volume-1 second (FEV1)/ forced vital capacity (FVC) was 82.8 ± 10.7%, ACQ score of 1.5 (0.8), and PAQLQ score of 5.5 (1.1).BMI was significantly directly correlated with ACQ score (r = 0.610, p &lt; 0.001), and inversely correlated with predicted FEV1/FVC (r = -0.537, p = 0.002) and PAQLQ score (r = -0.625, p &lt; 0.002). Conclusions: In obese asthmatic children, obesity is associated with a reduction in lung function and poor asthma control, and quality of life. Early weight-loss interventions could play role in preventing obesity and related pulmonary function impairment in asthmatic children.

Sevoflurane Postconditioning Inhibits Pulmonary Apoptosis via PI3K/AKT in Dog Cardiopulmonary Bypass Model

The study aimed to investigate the protective effects and regulatory mechanism of sevoflurane postconditioning (SPC) in pulmonary apoptosis induced by cardiopulmonary bypass (CPB). Twenty-four healthy dogs were divided into a control (C group), ischemia/reperfusion (I/R group), sevoflurane postconditioning (S group), and wortmannin group (S+W group). At 10 min after the establishment of CPB, the left pulmonary artery was blocked. When the pulmonary artery was reopened, 2% sevoflurane was administered. Wortmannin was delivered 10 min before the pulmonary artery was open. Before thoracotomy was implemented (T1), when the artery was reopened (T2) and 2 h after CPB (T3), blood and the inferior lobe of the left lung were isolated and subjected to gas analysis, pathological examination, western blot, and TUNEL staining. No obvious changes were observed in the C group throughout the experiment. The conditions of all treated groups progressively deteriorated, and no difference could be found except in the number of apoptotic cells of T3 between the S+W and I/R groups. At T2, the treated groups showed similar conditions. At T3, the lung function and structure of the S group were improved in I/R and S+W groups. The S group showed the highest p-Akt expression, the lowest cleaved-caspase 3 expression, and apoptotic cell percentage. Ischemia-reperfusion of the lung during CPB reduces lung function and injures the pulmonary structure via inducing lung apoptosis. Sevoflurane postconditioning preserves lung function and structure by alleviating apoptosis via activation of PI3K/Akt.

A Pilot Randomized Trial of As-Needed Budesonide-Formoterol for Stepping Down Controller Treatment in Moderate Asthma with Complete Remission.

BackgroundThe use of low-dose inhaled corticosteroid-formoterol as reliever monotherapy has recently been recommended in the asthma treatment guidelines. However, the efficacy of this treatment strategy has not yet been determined during the stepping-down period in moderate asthma. This study aimed to evaluate the feasibility of reducing treatment to as-needed budesonide-formoterol (BFM) in moderate asthma with complete remission.MethodsWe randomly assigned 31 patients (8 males and 23 females with a mean age of 57.2 years) with complete remission of asthma by inhaled BFM (160/4.5 μg) twice daily to receive BFM (160/4.5 μg) as needed (16 patients), or budesonide (BUD) (200 μg) twice daily (15 patients). The study was an open-label study done for 48 weeks, with the primary outcome as the cumulative percentages of patients with treatment failure (asthma exacerbation or loss of asthma control or lack of satisfaction after using medications) in the two groups.ResultsSix patients (42%) using as-needed BFM had treatment failure, as compared with three patients (21.4%) using BUD maintenance (hazards ratio for as-needed BFM, 1.77; 95% confidential interval, 0.44–7.12; p=0.41). The changes in forced expiratory volume in 1 second were −211.3 mL with as-needed BFM versus −97.8 mL with BUD maintenance (difference, 113.5 mL; p=0.75) and the change in fractional exhaled nitric oxide was significantly higher in both groups, at 8.68 parts per billion (ppb) in the as-needed BFM group and 2.5 ppb. in the BUD maintenance group (difference, 6.18 ppb; p=0.049).ConclusionCompared with BUD maintenance, there were no significant differences in treatment failure rate in patients who received as-needed BFM during the stepping down period in moderate asthma. However, they showed reduced lung function and relapsed airway inflammation. The results are limited by imprecision, and further large RCTs are needed.

SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2.

As of January 2022, at least 60 million individuals are estimated to develop post-acute sequelae of SARS-CoV-2 (PASC) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While elevated levels of SARS-CoV-2-specific T cells have been observed in non-specific PASC, little is known about their impact on pulmonary function which is compromised in the majority of these individuals. This study compares frequencies of SARS-CoV-2-specific T cells and inflammatory markers with lung function in participants with pulmonary PASC and resolved COVID-19 (RC). Compared to RC, participants with respiratory PASC had between 6- and 105-fold higher frequencies of IFN-γ- and TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells in peripheral blood, and elevated levels of plasma CRP and IL-6. Importantly, in PASC participants the frequency of TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells, which exhibited the highest levels of Ki67 indicating they were activity dividing, correlated positively with plasma IL-6 and negatively with measures of lung function, including forced expiratory volume in one second (FEV1), while increased frequencies of IFN-γ-producing SARS-CoV-2-specific T cells associated with prolonged dyspnea. Statistical analyses stratified by age, number of comorbidities and hospitalization status demonstrated that none of these factors affect differences in the frequency of SARS-CoV-2 T cells and plasma IL-6 levels measured between PASC and RC cohorts. Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms. These findings also provide mechanistic insight on the pathophysiology of PASC that can inform development of potential treatments to reduce symptom burden.

Inflammation resolution in environmental pulmonary health and morbidity

Inflammation and resolution are dynamic processes comprised of inflammatory activation and neutrophil influx, followed by mediator catabolism and efferocytosis. These critical pathways ensure a return to homeostasis and promote repair. Over the past decade research has shown that diverse mediators play a role in the active process of resolution. Specialized pro-resolving mediators (SPMs), biosynthesized from fatty acids, are released during inflammation to facilitate resolution and are deficient in a variety of lung disorders. Failed resolution results in remodeling and cellular deposition through pro-fibrotic myofibroblast expansion that irreversibly narrows the airways and worsens lung function. Recent studies indicate environmental exposures may perturb and deregulate critical resolution pathways.Environmental xenobiotics induce lung inflammation and generate reactive metabolites that promote oxidative stress, injuring the respiratory mucosa and impairing gas-exchange. This warrants recognition of xenobiotic associated molecular patterns (XAMPs) as new signals in the field of inflammation biology, as many environmental chemicals generate free radicals capable of initiating the inflammatory response. Recent studies suggest that unresolved, persistent inflammation impacts both resolution pathways and endogenous regulatory mediators, compromising lung function, which over time can progress to chronic lung disease. Chronic ozone (O3) exposure overwhelms successful resolution, and in susceptible individuals promotes asthma onset. The industrial contaminant cadmium (Cd) bioaccumulates in the lung to impair resolution, and recurrent inflammation can result in chronic obstructive pulmonary disease (COPD). Persistent particulate matter (PM) exposure increases systemic cardiopulmonary inflammation, which reduces lung function and can exacerbate asthma, COPD, and idiopathic pulmonary fibrosis (IPF). While recurrent inflammation underlies environmentally induced pulmonary morbidity and may drive the disease process, our understanding of inflammation resolution in this context is limited. This review aims to explore inflammation resolution biology and its role in chronic environmental lung disease(s).