Normal Lung Function Research Articles

Mesenchymal Stem Cells from COPD Patients Are Capable of Restoring Elastase-Induced Emphysema in a Murine Experimental Model

COPD is a chronic lung disease that affects millions of people, declining their lung function and impairing their life quality. Despite years of research and drug approvals, we are still not capable of halting progression or restoring normal lung function. Mesenchymal stem cells (MSC) are cells with extraordinary repair capacity, and MSC-based therapy brings future hope for COPD treatment, although the best source and route of administration are unclear. MSC from adipose tissue (AD-MSC) represents an option for autologous treatment; however, they could be less effective than donor MSC. We compared in vitro behavior of AD-MSC from COPD and non-COPD individuals by migration/proliferation assay, and tested their therapeutic potential in an elastase mouse model. In addition, we tested intravenous versus intratracheal routes, inoculating umbilical cord (UC) MSC and analyzed molecular changes by protein array. Although COPD AD-MSC have impaired migratory response to VEGF and cigarette smoke, they were as efficient as non-COPD in reducing elastase-induced lung emphysema. UC-MSC reduced lung emphysema regardless of the administration route and modified the inflammatory profile in elastase-treated mice. Our data demonstrate equal therapeutic potential of AD-MSC from COPD and non-COPD subjects in the pre-clinical model, thus supporting their autologous use in disease.

Effect of wheeze and lung function on lung sound parameters in children with asthma

BackgroundIn children with asthma, there are many cases in which wheeze is confirmed by auscultation with a normal lung function, or in which the lung function is decreased without wheeze. Using an objective lung sound analysis, we examined the effect of wheeze and the lung function on lung sound parameters in children with asthma. MethodsA total of 114 children with asthma (males to females = 80: 34, median age 10 years old) were analyzed for their lung sound parameters using conventional methods, and wheeze and the lung function were checked. The effects of wheeze and the lung function on lung sound parameters were examined. ResultsThe patients with wheeze or decreased forced expiratory flow and volume in 1 s (FEV1) (% pred) showed a significantly higher sound power of respiration and expiration-to-inspiration sound power ratio (E/I) than those without wheeze and a normal FEV1 (% pred). There was no marked difference in the sound power of respiration or E/I between the patients without wheeze and a decreased FEV1 (% pred) and the patients with wheeze and a normal FEV1 (% pred). ConclusionsOur data suggest that bronchial constriction in the asthmatic children with wheeze similarly exists in the asthmatic children with a decreased lung function. A lung sound analysis is likely to enable an accurate understanding of airway conditions.

Structural features on quantitative chest computed tomography of patients with maximal mid-expiratory flow impairment in a normal lung function population

BackgroundMaximal mid-expiratory flow (MMEF) is an earlier predictor of chronic obstructive pulmonary disease (COPD) development than forced expiratory volume in 1 s (FEV1). Changes of lung structure in patients with MMEF impairment only is still not clear. Therefore, this study aimed to investigate the structural features of patients with decreased MMEF by quantitative computed tomography (QCT) and develop a predictive model for predicting patients with reduced MMEF in normal lung function population.MethodsIn this study, 131 patients with normal spirometry results and available volumetric chest CT images were enrolled and divided into the reduced MMEF group (FEV1/forced expiratory vital capacity (FEV1/FVC) > 0.7, FEV1% predictive values (FEV1%pred) > 80%, MMEF%pred < 80%, n = 52) and the normal MMEF group (FEV1/FVC > 0.7, FEV1%pred > 80%, MMEF%pred ≥ 80%, n = 79). The emphysema, small airway disease and medium-size airway parameters were measured by a commercial software. The differences were investigated in clinical features, spirometrical parameters and QCT parameters between the two groups. A nomogram model was constructed based on the results of the multivariable logistic regression model. Spearman’s correlation coefficients were calculated between QCT measurements and spirometrical parameters.ResultsThere were more males in reduced MMEF group than normal group (P < 0.05). Lung parenchyma parameter (PRMEmph) and airway-related parameters (functional small airway disease (PRMfSAD), luminal area of fifth- and sixth- generation airway (LA5, LA6) were significantly different between the reduced MMEF group and the normal group (20.2 ± 17.4 vs 9.4 ± 6.7, 3.4 ± 3.5 vs 1.9 ± 2.0, 12.2 ± 2.5 vs 13.7 ± 3.4, 7.7 ± 2.4 vs 8.9 ± 2.8, respectively, all P < 0.01). After multivariable logistical regression, only sex (odds ratio [OR]: 2.777; 95% confidence interval [CI]:1.123–3.867), PRMfSAD (OR:1.102, 95%CI:1.045–1.162) and LA6 (OR:0.650, 95%CI:0.528–0.799) had significant differences between the two groups (P < 0.05) and a model incorporating with the three indicators was constructed (area under curve, 0.836). Correlation analysis showed MMEF%pred had mild to moderate correlation with airway-related measurements.ConclusionIn normal lung function population, patients with reduced MMEF have potential medium-size and small airway changes, and MMEF%pred is significantly associated with airway-related CT parameters. The nomogram incorporating with sex, PRMfSAD and LA6 has good predictive value and offers more objective evidences in a group with reduced MMEF.

Pregnancy Outcomes in Patients With Interstitial Lung Disease.

Women with interstitial lung disease (ILD) are recommended to avoid pregnancy based on limited data. This study seeks to determine maternal and pregnancy outcomes in the largest-to-date cohort of patients with ILD. Medical records in the Duke University Health System were reviewed for pregnancies in patients with a diagnosis of ILD with underlying autoimmune disease. Pregnancies were classified as having very severe, severe, mild-moderate, or normal lung function based on pulmonary function tests (PFTs). Adverse pregnancy outcomes (APOs) were defined using the Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus and Antiphospholipid Syndrome APO (PROMISSE-APO) and Severe PROMISSE-APO criteria. Among 86 pregnancies in 60 women, 85% women were Black, 71% had sarcoidosis, and 29% had connective tissue disease (CTD)-associated ILD (CTD-ILD). Of the pregnancies with available PFTs (n = 59), 12% had very severe ILD, 25% had severe ILD, 51% had mild-moderate ILD, and 12% had normal lung function. PROMISSE-APOs occurred in 32% of pregnancies, including all pregnancies with very severe ILD (P= 0.02 across severity groups), 56% of pregnancies with CTD-ILD, and 23% with sarcoidosis (P= 0.02). Severe PROMISSE-APOs occurred in 15% of pregnancies, including 60% with very severe ILD and 28% with CTD-ILD. There were no maternal deaths. One woman required an intensive care hospital stay during pregnancy. Three women had volume overload after delivery that resolved with medical management. Seven women received oxygen during delivery, although none were intubated. Although APOs were common in women with very severe ILD and underlying CTD, overall maternal morbidity and mortality were low. These data suggest women with ILD may be able to safely attempt pregnancy.

Antioxidant and Pulmonary Protective Potential of Fraxinus xanthoxyloides Bark Extract against CCl4 -Induced Toxicity in Rats.

Fraxinus xanthoxyloides is a perennial shrub belonging to family Oleaceae, traditionally used for malaria, jaundice, pneumonia, inflammation, and rheumatism. Our study is aimed to assess the total phenolics (TPC), flavonoids (TFC), terpenoids contents (TTC) and antioxidant profiling of F. xanthoxyloides methanol bark extract (FXBM) and its fractions, hexane, chloroform, ethyl acetate and aqueous, along with high-performance liquid chromatography with diode-array detection (HPLC-DAD). Further, the antioxidant and pulmonary protective potential was explored against carbon tetrachloride (CCl4 )-induced CCl4-induced pulmonary tissue damage in rats. The highest TPC, TFC and TTC were found in FXBM (133.29±4.19 mg/g), ethyl acetate fraction (279.55±10.35 mg/g), and chloroform fraction (0.79±0.06 mg/g), respectively. The most potent antioxidant capacity was depicted by FXBM (29.21±2.40 μg/mg) and ethyl acetate fraction (91.16±5.51 μg/mg). The HPLC-DAD analysis revealed the predominance of gallic, chlorogenic, vanillic and ferulic acid in FXBM. The administration of CCl4 induced oxidative stress, suppressed antioxidant enzymes' activities including catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, and glutathione reductase. Further, it increased thiobarbituric acid reactive substances (TBARS) and H2 O2 levels, induced DNA injuries and reduced the total protein and glutathione content in lung tissues. The treatment of rats with FXBM restored these biochemical parameters to the normal level. Moreover, the histopathological studies of lung tissues demonstrated that FXBM protected rats' lung tissues from oxidative damage restoring normal lung functions. Thus, F. xanthoxyloides bark extract is recommended as adjuvant therapy as protective agent for patients with lung disorders.

Association between preserved ratio impaired spirometry and sleep apnea in a Chinese community

Objective This study investigated the association between obstructive sleep apnea (OSA) and preserved ratio impaired spirometry (PRISm) in a community population. Methods Baseline data from a prospective cohort study, the Predictive Value of Combining Inflammatory Biomarkers and Rapid Decline of FEV1 for COPD (PIFCOPD), were used for cross-sectional analysis. Participants aged 40–75 years were recruited from the community and their demographic information and medical history were collected. The STOP-Bang questionnaire (SBQ) was used to assess the risk of OSA. Pulmonary function tests were performed using a portable spirometer (COPD-6) and forced expiratory volume in 1 s (FEV1) and 6 s (FEV6) were measured. Routine blood, biochemical, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 tests were also performed. The pH of the exhaled breath condensate was determined. Results A total of 1183 participants were enrolled, of which 221 with PRISm and 962 with normal lung function. The neck circumference, waist-to-hip ratio, hs-CRP concentration, proportion of males, cigarette exposure, number of current smoker, high risk of OSA, and prevalence of nasal and ocular allergy symptoms were significantly higher in the PRISm group than in the non-PRISm group (p < .05). Logistic regression showed that the risk of OSA (odds ratio, 1.883; 95% confidence interval, 1.245–2.848), waist-to-hip ratio, current smoking, and prevalence of nasal allergy symptoms were independently associated with PRISm after correcting for age and sex. Conclusion These findings showed that OSA prevalence is independently associated with PRISm prevalence. Further studies should confirm the relationship between systemic inflammation in OSA, localized inflammation of the airways, and impaired lung function.

Circulating levels of mitochondrial oxidative stress-related peptides MOTS-c and Romo1 in stable COPD: A cross-sectional study.

MOTS-c and Romo1 are mitochondrial peptides that are modulated by oxidative stress. No previous studies have explored circulating levels of MOTS-c in patients with chronic obstructive pulmonary disease (COPD). We enrolled 142 patients with stable COPD and 47 smokers with normal lung function in an observational cross-sectional study. We assessed serum levels of both MOTS-c and Romo1 and associated these findings with clinical characteristics of COPD. Compared with smokers with normal lung function, patients with COPD had lower levels of MOTS-c (p = 0.02) and higher levels of Romo1 (p = 0.01). A multivariate logistic regression analysis revealed that above-median MOTS-c levels were positively associated with Romo1 levels (OR 1.075, 95% CI 1.005-1.150, p = 0.036), but no association was found with other COPD characteristics. Below-median levels of circulating MOTS-c were associated with oxygen desaturation (OR 3.25 95% CI 1.456-8.522, p = 0.005) and walking <350 meters (OR 3.246 95% CI 1.229-8.577, p = 0.018) in six-minute walk test. Above-median levels of Romo1 were positively associated with current smoking (OR 2.756, 95% CI 1.133-6.704, p = 0.025) and negatively associated with baseline oxygen saturation (OR 0.776 95% CI 0.641-0.939, p = 0.009). Reduced levels of circulating MOTS-c and increased levels of Romo1 were detected in patients diagnosed with COPD. Low levels of MOTS-c were associated with oxygen desaturation and poorer exercise capacity using 6 min walk test. Romo1 was associated with current smoking and baseline oxygen saturation. www.clinicaltrials.gov; No.: NCT04449419; URL: www.clinicaltrials.gov. Date of registration: June 26, 2020.

Lung Inflammation in alpha-1-antitrypsin deficient individuals with normal lung function

BackgroundAlpha-1-antitrypsin deficient (AATD) individuals are prone to develop early age of onset chronic obstructive pulmonary disease (COPD) more severe than non-genetic COPD. Here, we investigated the characteristics of lower respiratory tract of AATD individuals prior to the onset of clinically significant COPD.MethodsBronchoalveolar lavage was performed on 22 AATD with normal lung function and 14 healthy individuals. Cell counts and concentrations of proteases, alpha-1-antitrypsin and proinflammatory mediators were determined in the bronchoalveolar lavage fluid from study subjects. In order to determine the airway inflammation, we also analyzed immune cell components of the large airways from bronchial biopsies using immunohistochemistry in both study subjects. Finally, we made comparisons between airway inflammation and lung function rate of decline using four repeated lung function tests over one year in AATD individuals.ResultsAATD individuals with normal lung function had 3 folds higher neutrophil counts, 2 folds increase in the proteases levels, and 2–4 folds higher levels of IL-8, IL-6, IL-1β, and leukotriene B4 in their epithelial lining fluid compared to controls. Neutrophil elastase levels showed a positive correlation with the levels of IL-8 and neutrophils in AATD epithelial lining fluid. AATD individuals also showed a negative correlation of baseline FEV1 with neutrophil count, neutrophil elastase, and cytokine levels in epithelial lining fluid (p < 0.05). In addition, we observed twofold increase in the number of lymphocytes, macrophages, neutrophils, and mast cells of AATD epithelial lining fluid as compared to controls.ConclusionMild inflammation is present in the lower respiratory tract and airways of AATD individuals despite having normal lung function. A declining trend was also noticed in the lung function of AATD individuals which was correlated with pro-inflammatory phenotype of their lower respiratory tract. This results suggest the presence of proinflammatory phenotype in AATD lungs. Therefore, early anti-inflammatory therapies may be a potential strategy to prevent progression of lung disease in AATD individuals.

Decreased expression of surfactant Protein-C and CD74 in alveolar epithelial cells during influenza virus A(H1N1)pdm09 and H3N2 infection

The primary replication site of Influenza A virus (IAV) is type II alveolar epithelial cells (AECII), which are central to normal lung function and present important immune functions. Surfactant components are synthesized primarily by AECII, which play a crucial role in host defense against infection.The aim of this study was to analyze if the impact of influenza infection is differential between A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) on costimulatory molecules and ProSP-C expression in AECII from BALB/c mice infected and A549 cell line infected with both strains.Pandemic A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) were used to infect BALB/c mice and the A549 cell line. We evaluated the surface expression of co-stimulatory molecules (CD45/CD31/CD74/ProSP-C) in AECII and A549 cell lines. Our results showed a significant decrease in ProSP-C+ CD31− CD45– and CD74+ CD31− CD45− expression in AECII and A549 cell line with the virus strain A(H1N1)pdm09 versus A/Victoria/3/75 (H3N2) and controls (non-infection conditions).Our findings indicate that changes in the expression of ProSP-C in AECII and A549 cell lines in infection conditions could result in dysfunction leading to decreased lung compliance, increased work of breathing and increased susceptibility to injury.

Effectiveness of Benralizumab in OCS-Dependent Severe Asthma: The Impact of 2 Years of Therapy in a Real-Life Setting.

In this retrospective study, we evaluated the effects of 2 years of treatment with benralizumab on 44 patients with OCS-dependent severe asthma by analyzing clinical, biological and functional data. After 2 years of benralizumab, 59.4% discontinued OCS and patients who continued to use OCS had their mean dose reduced by approximately 85% from baseline. Meanwhile, 85% of patients had their asthma well-controlled (ACT score > 20) and had no exacerbations, and 41.6% had normal lung function. Our findings support the long-term effectiveness of benralizumab in severe OCS-dependent asthma in a real-life setting, suggesting potential reductive effects on costs and complications such as adverse pharmacological events.

Allergic bronchopulmonary aspergillosis in identical twins: Effectiveness of dupilumab

Allergic bronchopulmonary aspergillosis in identical twins: Effectiveness of dupilumab

Effect of safety and hygiene practices on lung function among Indonesian farmers exposed to pesticides

Aim: This study aimed to detect lung function impairment in farmers exposed to pesticides related to safety and hygiene practices in pesticide application. Methods: This was a cross-sectional study with respondents are 200 farmers who were exposed to pesticides in Grobogan, the main agricultural center in Central Java, Indonesia, which has 95.75% agricultural workers. Data were collected by a questionnaire-based interview, observation, and spirometry measurement. Chi-square and Multinomial Regression were used for the statistical test. Results: The survey results of all respondents showed that 12% had restriction lung function, 32% had obstruction lung function, and 56% had normal lung function. There was a significant effect between work period, pesticide spraying hour per day, spraying against wind direction, changing clothes directly after exposure to pesticides, taking a bath directly after exposure to pesticides with "farmer's lung function" based on statistical test results. Conclusion: The Safety and hygiene practices of farmers exposed to pesticides could affect their lung function. It is suggested that to improve management and regulation control of pesticide application, educational programs and reinforcement of "safety and hygiene practices" in the workplace as effective approaches for preventing respiratory disorders related to pesticide exposures.

Identification of Asthma Phenotypes in the Spanish MEGA Cohort Study Using Cluster Analysis

IntroductionThe definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes. MethodsWe performed a multicentre prospective cohort study, including adult patients with asthma (N=512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A standardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm. ResultsFour clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities. ConclusionWe defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps.

In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma

Alveolar macrophages (AMs) are crucial for maintaining normal lung function. They are abundant in lung cancer tissues, but their pathophysiological significance remains unknown. Here we show, using an orthotopic murine lung cancer model and human carcinoma samples, that AMs support cancer cell proliferation and thus contribute to unfavourable outcome. Inhibin beta A (INHBA) expression is upregulated in AMs under tumor-bearing conditions, leading to the secretion of activin A, a homodimer of INHBA. Accordingly, follistatin, an antagonist of activin A is able to inhibit lung cancer cell proliferation. Single-cell RNA sequence analysis identifies a characteristic subset of AMs specifically induced in the tumor environment that are abundant in INHBA, and distinct from INHBA-expressing AMs in normal lungs. Moreover, postnatal deletion of INHBA/activin A could limit tumor growth in experimental models. Collectively, our findings demonstrate the critical pathological role of activin A-producing AMs in tumorigenesis, and provides means to clearly distinguish them from their healthy counterparts.

Follow-up of patients with a 5-year survival after paraquat poisoning using computed tomography images and spirometry.

The study aimed to examine long-term survival of patients with acute paraquat poisoning using computed tomography (CT) images and spirometry. A total of 36 patients with long-term survival after paraquat poisoning were followed-up and divided into mild (11 patients), moderate (17 patients), and severe (8 patients) paraquat poisoning groups. Differences among the groups were compared using clinical indicators, such as peripheral capillary oxygen saturation, arterial partial pressure of oxygen and 6-min walk test (6-MWT), chest CT, spirometry, and serum immunoglobulin E (IgE). The 6-MWT distance was significantly shorter in the severe paraquat poisoning group than that in the mild and moderate paraquat poisoning groups. In the mild paraquat poisoning group, CT revealed no obvious lung injury, and spirometry showed normal lung function in most patients. In moderate or severe paraquat poisoning group, CT images showed fibrotic lesions as cord-like high-density shadows, reticulations, and honeycombs. In addition, other pulmonary changes, including bronchiectasis, increased lung transparency, and pulmonary bullae, were discovered. In moderate or severe paraquat poisoning group, obvious obstructive ventilation dysfunction with slight restrictive and diffuse impairment were observed in some patients, with positive bronchial relaxation test and high serum IgE level. In the long-term follow-up, patients with severe paraquat poisoning showed the lowest exercise endurance. In moderate or severe paraquat poisoning group, CT images revealed diversified changes, not only dynamic evolution of pulmonary fibrosis process, but also signs of bronchiectasis, and chronic obstructive pulmonary disease. Some patients with moderate or severe paraquat poisoning developed obstructive ventilatory dysfunction with airway hyperresponsiveness.

A study of airflow patterns among patients attending a hospital set up in Manipur

Background: Clinicians and surgeons often require instant knowledge of the lung function of their patients during the course of their management though they rely on the symptoms most of the time. Yet unexpected, abnormal respiratory airflow patterns are found in various diseases which affect the management whereas many respiratory complaints used to turn out to be normal. Respiratory symptoms often but not always correlate with airflow abnormality, thus making office spirometry an important tool for addressing these problems. Aims and Objectives: An evaluation of the profile of airflow patterns observed among patients attending regional institute of medical sciences (RIMS) hospital, Manipur, is carried out. Materials and Methods: The spirometry test performances of total 221 patients (120 males and 101 females) aged between 11 and 80 years sent from outpatient and wards of different departments of our hospital (RIMS Imphal, Manipur) were done after taking informed consents. The period of test performance was from June 2016 to November 2018 on all working days in the department of physiology. For this, a computerized spirometer (Helios model no. 401) was used. Results: 176 (79.6% of the total studied) patients presented with symptoms of respiratory diseases and after spirometry test, 121 (54.7% of the total) were having different patterns of abnormal airflow. About 60% of 111 patients complaining only of breathlessness are found to have normal lung function. Among 13 patients with a common disease such as chronic obstructive pulmonary disease, unexpectedly 2 cases of restrictive type of airflow and another 2 patients with normal airflow were found. Conclusion: Awareness of such altered and unexpected occurrence in lung spirometry epidemiology would be informative to the physicians in disease management.

Effect of incentive spirometry on pulmonary function test in post COVID-19 pneumonia patients

Background. COVID-19 caused by SARS-CoV-2 virus was assigned as a pandemic by WHO. Fever, breathlessness, cough and expectoration indicates lung involvement in the form of pneumonia and its most common complications are pulmonary fibrosis, chronic respiratory failure and reduced quality of life. Incentive spirometry is the relevant therapy to enhance the normal lung function and improve quality of life. Aim. To find the effect of incentive spirometry on pulmonary function test in post COVID-19 pneumonia patients. Methodology. An experimental study with simple random sampling (lottery method) of 24 patients in age group (18-68 years). The participants were randomly divided into 2 groups. Group A received pharmacotherapy and incentive spirometry and Group B received only pharmacotherapy. Computerized spirometry and Diffusion lung capacity for carbon monoxide (DLCO) was used as diagnostic tool to measure pre &amp; post test values for both groups. Intervention was given for 4 weeks and after 4 weeks, to analyze the spirometry values post-test was taken for both groups. Outcome measures. Forced expiratory volume in the first second (FEV1), Forced vital capacity (FVC), FEV1/FVC &amp;DLCO. Results. Statistical analysis shows significant improvement (p &lt; 0.05) between pretest and post test values on Pulmonary Function Tests (PFT) in both Group A&amp;B whereas there was increase in the improvement in intervention group than control group. Conclusion. Incentive spirometry improved the lung volume and capacities on PFT in post COVID-19 pneumonia patients and also these patients have mainly restrictive lung pattern by the use of DLCO.

Impact of occupational asthma on health and employment status: a long-term follow-up study

ObjectivesThe aim of this study was to assess the predictors of a favourable prognosis of occupational asthma (OA) and the employment status of patients with OA at least 2 years...

Comparison of National and Global Asthma Management Guiding Documents.

Asthma is a common chronic disease that affects both adults and children, and that continues to have a high economic burden. Asthma management guidelines were first developed nearly 30 years ago to standardize care, maintain asthma control, improve quality of life, maintain normal lung function, prevent exacerbations, and prevent asthma mortality. The two most common asthma guidelines used today were developed by the National Asthma Education and Prevention Program (NAEPP) Expert Panel Working Group and the Global Initiative for Asthma Science Committee. Both guiding documents use scientific methodology to standardize their approach for formulating recommendations based on pertinent literature. Before the 2020 National Asthma Education and Prevention Program (Expert Panel Report 4), nothing had been released since the 2007 guidelines, whereas the Global Initiative for Asthma publishes updates annually. Although each of these asthma strategies is similar, there are some noted differences. Over the years, the focus of asthma treatment has shifted from acute to chronic management. Frontline respiratory therapists and other health-care providers should have a good understanding of these 2 guiding references and how they can impact acute and chronic asthma management. The primary focus of this narrative is to look at the similarities and differences of these 2 guiding documents as they pertain to the 6 key questions identified by the Expert Panel of the National Asthma Education and Prevention Program.

Topography of pleural epithelial structure enabled by en face isolation and machine learning.

Pleural epithelial adaptations to mechanical stress are relevant to both normal lung function and parenchymal lung diseases. Assessing regional differences in mechanical stress, however, has been complicated by the nonlinear stress-strain properties of the lung and the large displacements with ventilation. Moreover, there is no reliable method of isolating pleural epithelium for structural studies. To define the topographic variation in pleural structure, we developed a method of en face harvest of murine pleural epithelium. Silver-stain was used to highlight cell borders and facilitate imaging with light microscopy. Machine learning and watershed segmentation were used to define the cell area and cell perimeter of the isolated pleural epithelial cells. In the deflated lung at residual volume, the pleural epithelial cells were significantly larger in the apex (624 ± 247 μm2 ) than in basilar regions of the lung (471 ± 119 μm2 ) (p < 0.001). The distortion of apical epithelial cells was consistent with a vertical gradient of pleural pressures. To assess epithelial changes with inflation, the pleura was studied at total lung capacity. The average epithelial cell area increased 57% and the average perimeter increased 27% between residual volume and total lung capacity. The increase in lung volume was less than half the percent change predicted by uniform or isotropic expansion of the lung. We conclude that the structured analysis of pleural epithelial cells complements studies of pulmonary microstructure and provides useful insights into the regional distribution of mechanical stresses in the lung.