Impaired Pulmonary Function Research Articles

Correction of severe adult idiopathic scoliosis posteriorly with skipped pedicle screw instrumentation and rod augmentation.

Although it is challenging to correct severe adult idiopathic scoliosis (ADIS) deformities, optimal results can be achieved by multiple asymmetric Ponte osteotomies with lower surgical risks. Skipping the apical instrumentation and using multiple rods and connectors may further facilitate the procedure. We named this method as "modular correction technique" (MCT). Sixty-two patients with severe ADIS who were treated with MCT were recruited into this study, and retrospectively evaluated. Radiographic and functional outcomes as well as pulmonary functions were examined preoperatively and at last follow-up. Main radiologic parameters were related to Cobb angles, coronal, sagittal, and shoulder balance. Scoliosis Research Society-22 questionnaire and the Oswestry Disability Index were used to evaluate clinical outcomes. Average age of the patients was 41.3 years (range: 23-65). Thirty-nine of the patients were female and 23 of them were male. Coronal Cobb angle of the main curve, shoulder balance, coronal, and sagittal balance significantly improved after the surgery. Forced vital capacity and forced expiratory volume in the first second were mildly improved after the surgery, however the improvement was not statistically significant. Postoperative clinical outcome scores improved significantly. MCT can be performed with low risk of complications and relatively low operation time and blood loss. It facilitates rod insertion and correction maneuvers. Radiologic, especially coronal balance, and functional outcomes can be improved with minimal morbidity while deterioration of pulmonary function is prevented. This technique is useful in severe but relatively flexible ADIS deformities.

Paired ATAC- and RNA-seq offer insight into the impact of HIV on alveolar macrophages: a pilot study

People with HIV remain at greater risk for both infectious and non-infectious pulmonary diseases even after antiretroviral therapy initiation and CD4 cell count recovery. These clinical risks reflect persistent HIV-mediated defects in innate and adaptive immunity, including in the alveolar macrophage, a key innate immune effector in the lungs. In this proof-of-concept pilot study, we leveraged paired RNA-seq and ATAC-seq analyses of human alveolar macrophages obtained with research bronchoscopy from people with and without HIV to highlight the potential for recent methodologic advances to generate novel hypotheses about biological pathways that may contribute to impaired pulmonary immune function in people with HIV. In addition to 35 genes that were differentially expressed in macrophages from people with HIV, gene set enrichment analysis identified six gene sets that were differentially regulated. ATAC-seq analysis revealed 115 genes that were differentially accessible for people with HIV. Data-driven integration of the findings from these complementary, high-throughput techniques using xMWAS identified distinct clusters involving lipoprotein lipase and inflammatory pathways. By bringing together transcriptional and epigenetic data, this analytic approach points to several mechanisms, including previously unreported pathways, that warrant further exploration as potential mediators of the increased risk of pulmonary disease in people with HIV.

One-fourth of COVID-19 patients have an impaired pulmonary function after 12 months of disease onset.

There is increasing data that show a persistently impaired pulmonary function upon recovery after severe infection. Little is known however about the extent, recovery and determinants of pulmonary impairment across the full spectrum of COVID-19 severity over time. In a well characterized, prospective cohort of both hospitalised and non-hospitalised individuals with SARS-CoV-2 infection, the RECoVERED study, pulmonary function (diffusing capacity for carbon monoxide (DLCO)) and spirometry) was measured until one year after disease onset. Additionally, data on sociodemographics, clinical characteristics, symptoms, and health-related quality of life (HRQL) were collected. Pulmonary function and these determinants were modelled over time using mixed-effect linear regression. Determinants of pulmonary function impairment at 12 months after disease onset were identified using logistic regression. Between May 2020 and December 2021, 301 of 349 participants underwent at least one pulmonary function test. After one year of follow-up, 25% of the participants had an impaired pulmonary function which translates in 11%, 22%, and 48% of the participants with mild, moderate and severe/critical COVID-19. Improvement in DLCO among the participants continued over the period across one, six and twelve months. Being older, having more than three comorbidities (p<0·001) and initial severe/critical disease (p<0·001) were associated with slower improvement of pulmonary function over time, adjusted for age and sex. HRQL improved over time and at 12 months was comparable to individuals without impaired pulmonary function. The prevalence of impaired pulmonary function after twelve months of follow-up, was still significant among those with initially moderate or severe/critical COVID-19. Pulmonary function increased over time in most of the severity groups. These data imply that guidelines regarding revalidation after COVID-19 should target individuals with moderate and severe/critical disease severities.

Utility of fibroblasts derived from broncho-alveolar lavage of patients with idiopathic pulmonary fibrosis or related disorders to develop in vitro models

Broncho-alveolar lavage (BAL) represents a safe tool for the differential diagnosis of various pulmonary fibrotic diseases. Idiopathic pulmonary fibrosis (IPF) belongs to a heterogeneous group of diseases, interstitial lung disease (ILD), presenting a progressive impairment of pulmonary functions. IPF is characterized by the excessive accumulation of extracellular matrix (ECM) in the alveolar parenchyma that may lead to irreversible pulmonary remodeling. Although the exact pathogenetic mechanisms leading to IPF development are still unclear it has been demonstrated that fibroblasts differentiating toward myofibroblasts are the major actors involved in this process. The possibility of obtaining and expanding fibroblasts from the BAL of ILD patients for research purposes has been recently explored. This approach is discussed here as a reliable chance, helpful to advance the scientific community knowledge and to devise two- and three-dimensional (2D/3D) pre-clinical in vitro models of these diseases, further overcoming technical and ethical concerns related to the use of fibroblasts derived from tissue biopsy.

Pulmonary Artery Pressure Status in Hemodialysis Patients and Its Association with Nutritional and Biochemical Markers

Background: The prevalence of pulmonary hypertension (PH) is reported between 17% and 56% in hemodialysis patients. The pathogenesis of PH in hemodialysis patients is still unclear. Malnutrition may be associated with impaired pulmonary function in hemodialysis patients. Objectives: The present study aimed to investigate the association between PH and nutritional and biochemical markers in hemodialysis patients. Methods: In this cross-sectional study, 80 patients undergoing hemodialysis at the Kowsar Medical Center, Semnan, Iran, from 1 March 2016 to 31 August 2016 were enrolled by complete enumeration. Pulmonary artery pressure was determined by echocardiography between hemodialysis sessions. Arm circumference, triceps fat mass, and body mass index (BMI) were determined. Other laboratory tests included transferrin, serum albumin, cholesterol, triglyceride, and hemoglobin. The source of receiving protein was recorded in a questionnaire. The data were analyzed by the chi-square test and logistic regression analysis at a significance level of less than 0.05. Results: Pulmonary hypertension ( &gt; 25 mmHg) was found in 32 (40%) of the 80 patients studied. The mean of pulmonary pressure in patients with PH was 34.66 ± 5.6 mmHg compared to 16.85 ± 3.7 mmHg in patients without PH. Age, gender, arm circumference, frequency of dialysis per year, and serum levels of albumin, transferrin, triglyceride, and total cholesterol were not significantly different between patients with and without PH. There was a significant difference in the mean hemoglobin level between patients with and without PH (P = 0.003). The likelihood of developing PH was reduced by 0.3 in those with hemoglobin ≥ 11 g/dL compared to patients with hemoglobin levels below 11 g/dL (OR = 0.400, P = 0.003). The likelihood of developing PH in patients with albumin ≥ 3.8 g/L decreased by 0.126 compared to those with albumin less than 3.8 (OR = 0.126, P = 0.003). Conclusions: The results of our study indicated a higher incidence of PH in patients with lower levels of hemoglobin and albumin. So, patients undergoing hemodialysis are recommended to be regularly screened for these two variables.

Are Babies Born Preterm High-Risk Asthma Candidates?

Among preterm infants, the risk of developing asthma is a matter of debate. This review discusses the state of the art of poorly understood prematurity-associated asthma. Impaired pulmonary function is common in children born prematurely. Preterm infants are prone to developing viral respiratory tract infections, bronchiolitis in the first year of life, and recurrent viral wheezing in preschool age. All of these conditions may precede asthma development. We also discuss the role of both atopic sensitization and intestinal microbiome and, consequently, immune maturation. Diet and pollution have been considered to better understand how prematurity could be associated with asthma. Understanding the effect of factors involved in asthma onset may pave the way to improve the prediction of this asthma phenotype.

Moderate selenium alleviates the pulmonary function impairment induced by cadmium and lead in adults: A population-based study

Selenium (Se) has been reported to have an antagonistic effect on heavy metals in animals. However, there is no epidemiological study investigating whether Se could protect against the pulmonary toxicity of Cadmium (Cd) and Lead (Pb). Data was collected from the 2011–2012 National Health and Nutrition Examination Survey (NHANES) cycle. Pulmonary function was assessed by Forced Vital Capacity (FVC), Forced Expiratory Volume 1st Second (FEV1) and FEV1/FVC. Blood concentrations of Cd, Pb, and Se were measured using inductively coupled plasma mass spectrometry. Linear regression, restricted cubic splines, and quantile-based g-computation (qgcomp) were performed to evaluate the individual and joint associations of Cd and Pb with pulmonary function and whether Se modified these associations. In the adjusted multi-metal model, every 1-unit increase in Cd, FEV1, FVC, and FEV1/FVC decreased by 76.437 mL (95 % CI: −110.928 to −41.947), 42.719 mL (95 % CI: −84.553 to −0.885), and 0.012 (95 % CI: −0.016 to −0.007), respectively. Meanwhile, FEV1 decreased by 9.37 mL (95 % CI: −18.61 to −0.13) for every 1 unit increase in Pb. Furthermore, we found an inverted U-shape association between Se and lung function, and participants in the second quartile Se group had the highest increases in FEV1 and FVC compared with participants in the lowest quartile. Qgcomp model also revealed that the toxic metal mixture (Cd and Pb) exhibited a significant inverse association with FEV1 and FEV1/FVC. Furthermore, we found that the inverse association of Pb and Cd, either alone or in combination, with pulmonary function first diminished with increasing Se levels but was re-enforced when blood Se concentrations were in the highest quartile. Our results indicated that moderate Se attenuated the harmful effects of Cd and Pb on lung function.

Impact of lag time on lung function impairment in pulmonary tuberculosis sequelae patients – A cross-sectional study

Background: Treatment completed pulmonary tuberculosis (PTB) patients are often left with permanent pulmonary function impairment. Lag time remains a major factor in determining the severity of the sequelae. Aims and Objectives: This study aims to assess the impact of lag time on PTB sequelae. Materials and Methods: A cross-sectional study was conducted during July 2019–December 2020. A total of 85 patients presenting with clinicoradiological features of PTB sequelae were recruited for the study and spirometry and diffusion capacity of lungs (DLCO) were done. They were divided into study groups based on lag time. The lag time (in days) was considered as primary explanatory variable. One-way ANOVA and Chi-square tests were used. coGuide V.1.0 was used for statistical analysis. Results: The mean lag time was 52.94 days in the study population. The mean duration of after treatment was 15.45 years in the study population. There was a statistically significant difference across study groups (classified based on the lag time) in lung function such as FVC%, FEV1, FEVI/FVC, MEF, DLCO, and duration of after treatment (P&lt;0.05). Conclusion: The lag time from the development of symptom to the diagnosis of the disease has a significant impact on lung function impairment in PTB sequelae patients since the increase in lag time increases the severity of lung function impairment. Early identification and treatment may help in reducing the progression of lung function impairment.

Alcohol Dependence and Rib Fracture Outcomes: A Systematic Review and Meta-Analysis.

Chronic alcohol use has been associated with impaired pulmonary function, increased risk of pneumonia and poor outcomes after trauma. With a high incidence of rib fractures in this population, the clinical and physiological factors associated with alcohol dependence may influence how these patients recover from thoracic injuries. Therefore, the aim of the systematic review was to examine the effect of alcohol dependence on rib fracture outcomes. The Embase, PubMed and Web of Science databases were searched for studies examining adult patients with rib fractures, with and without a history of alcohol dependency. The outcomes of interest were mortality, pulmonary complications, intensive care length of stay, ventilator days and hospital length of stay. A meta-analysis was performed to combine the data and compare results. Three studies met the criteria for inclusion in the review and all studies were observational in design. Alcohol dependency was associated with increased mortality (OR 1.44 (95% CI: 1.33-1.56)), pneumonia (OR 2.14 (2.02-2.27)) and ARDS (OR 1.71(1.48-1.98)) as well as longer stays in hospital and intensive care (p<0.05). No difference was found in ventilator days between the two groups.Early intensive care review should be considered to reduce complications in this population alongside prompt management of withdrawal symptoms. However, limited primary research exists on this topic and the quality of current evidence is low. Additional primary research is needed to further understand this correlation and draw meaningful conclusions.

Associations between spirometric measures and exercise capacity in type 2 diabetes

BackgroundPhysical exercise aids glycemic control and the prevention of diabetes-related complications. However, exercise beyond an individual's pulmonary functional capacity may be detrimental. To date, little is known about the relationship between pulmonary function and exercise capacity in people with type 2 diabetes (T2D). We investigated the relationship between pulmonary function and exercise capacity in T2D. MethodsSpirometry and 6-min walk test (6MWT) were conducted for 263 systematically sampled adults with T2D without primary heart/lung disease. The primary measure of exercise capacity was the 6-min walk distance (6MWD); impaired exercise capacity was defined as 6MWD<400 m. Logistic regression analyses were used to assess the associations between spirometric measures and exercise capacity with adjustments for age, sex, height, body mass index, diabetes duration, glycated hemoglobin concentration, smoking, suboptimum blood pressure control, and total cholesterol concentration. ResultsCompared with individuals with normal spirometry, those with pulmonary restriction/obstruction had significantly lower 6MWD (404.67 m vs. 451.70),p < 0.001). The proportion of individuals with impaired exercise capacity was higher in individuals with impaired pulmonary function compared with those with normal pulmonary function (39.8% vs. 20.7%,p = 0.001). In the unadjusted models, decreasing Z-score FEV1 [odds ratio 1.40, 95% confidence interval (1.07–1.83),p = 0.013] and Z-score FVC [1.37 (1.06–1.76),0.016], but not Z-score FEV1/FVC ratio [1.00 (0.78–1.27),0.972] were significantly associated with impaired exercise capacity. In the fully adjusted model, the strength of association remained statistically significant for Z-score FEV1 [1.60 (1.06–2.41),0.025] but not Z-score FVC [1.48 (0.98–2.23),0.065]. ConclusionsOur study shows inverse associations between FEV1 and impaired exercise capacity in T2D, Future research could characterize optimal exercise levels based on a patient's FEV1.

Dust Exposure and Lung Function Disorders

Dust is a particle floating in the air produced due to mechanical processes such as splitting, grinding, grinding, punching or blasting, cutting and destroying material. Dust particles in the air for a relatively long time can enter the human body through breathing. Dust less than 5 µm entering the human respiratory system can reach the inside of the lungs or alveoli can cause lung function disorders. Impaired pulmonary function is the inability to develop (elasticity) of the lungs as well as disorders of the respiratory tract both structural (anatomical) and functional which causes slowing of respiratory airflow. The International Labor Organization (ILO) defines pulmonary dysfunction as the accumulation of dust in the lung tissue and lung tissue reaction to the dust accumulation. Dust entering the alveoli can cause hardening of the tissue (fibrosis) and if 10% of the alveoli is hardening, it will reduce its elasticity in accommodating the volume of air so that the ability to bind oxygen is decreased. This condition causes a reduction in the supply of oxygen absorbed by blood capillaries to the brain tissue, heart, and other body parts.

Association of Pulmonary Function with Osteosarcopenic Obesity in Older Adults Aged over 50 Years.

Osteosarcopenic obesity (OSO) is a newly described coexistence of osteopenia/osteoporosis, sarcopenia, and obesity. We examined the association between pulmonary function, OSO, and its composition in adults aged ≥ 50 years. A total of 26,343 participants (8640 men; 17,703 women) were classified into four groups based on the number of abnormal body compositions (osteopenia/osteoporosis, sarcopenia, and obesity): 0 (control), 1+, 2+, and 3+ (OSO) abnormal body compositions. The values of forced volume vital capacity (FVC)%, forced expiratory volume in 1 s (FEV1%), and FEV1/FVC% were significantly decreased by increasing the number of adverse body compositions (p < 0.0001). Although the prevalence of restrictive spirometry pattern (RSP) was positively associated with a higher number of abnormal body composition parameters (p < 0.001), obstructive spirometry pattern (OSP) had no association with adverse body composition. In multivariate analyses, the adjusted odds ratios (ORs) for RSP compared to the control group were 1.36 in 1+, 1.47 in 2+, and 1.64 in 3+ abnormal body compositions (p for trend < 0.001). Multiple abnormal body composition, especially osteosarcopenic obesity, was independently associated with poor lung function showing RSP in older adults over 50 years. The coexistence of these abnormal body compositions may be a predisposing factor for pulmonary function deterioration.

Systemic Markers of Lung Function and Forced Expiratory Volume in 1 Second Decline across Diverse Cohorts.

Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airway obstruction and accelerated lung function decline. Our understanding of systemic protein biomarkers associated with COPD remains incomplete. Objectives: To determine what proteins and pathways are associated with impaired pulmonary function in a diverse population. Methods: We studied 6,722 participants across six cohort studies with both aptamer-based proteomic and spirometry data (4,566 predominantly White participants in a discovery analysis and 2,156 African American cohort participants in a validation). In linear regression models, we examined protein associations with baseline forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC). In linear mixed effects models, we investigated the associations of baseline protein levels with rate of FEV1 decline (ml/yr) in 2,777 participants with up to 7 years of follow-up spirometry. Results: We identified 254 proteins associated with FEV1 in our discovery analyses, with 80 proteins validated in the Jackson Heart Study. Novel validated protein associations include kallistatin serine protease inhibitor, growth differentiation factor 2, and tumor necrosis factor-like weak inducer of apoptosis (discovery β = 0.0561, Q = 4.05 × 10-10; β = 0.0421, Q = 1.12 × 10-3; and β = 0.0358, Q = 1.67 × 10-3, respectively). In longitudinal analyses within cohorts with follow-up spirometry, we identified 15 proteins associated with FEV1 decline (Q < 0.05), including elafin leukocyte elastase inhibitor and mucin-associated TFF2 (trefoil factor 2; β = -4.3 ml/yr, Q = 0.049; β = -6.1 ml/yr, Q = 0.032, respectively). Pathways and processes highlighted by our study include aberrant extracellular matrix remodeling, enhanced innate immune response, dysregulation of angiogenesis, and coagulation. Conclusions: In this study, we identify and validate novel biomarkers and pathways associated with lung function traits in a racially diverse population. In addition, we identify novel protein markers associated with FEV1 decline. Several protein findings are supported by previously reported genetic signals, highlighting the plausibility of certain biologic pathways. These novel proteins might represent markers for risk stratification, as well as novel molecular targets for treatment of COPD.

Pulmonary function and structure abnormalities in children and young adults with osteogenesis imperfecta point to intrinsic and extrinsic lung abnormalities

PurposePulmonary disease is the major cause of morbidity and mortality in osteogenesis imperfecta (OI). We investigated the contribution of intrinsic lung factors to impaired pulmonary function in children and young...

Surviving Pulmonary Tuberculosis: Navigating the Long Term Respiratory Effects.

Tuberculosisis a transmissible disease caused by the bacteria Mycobacterium tuberculosis, which is a cause of significant morbidity and mortality all over the world. Tuberculosis has a number of risk factors, such as living in a developing country, poor ventilation, smoking, male sex, etc., which not only increase the chance of infection but may be independent factors for impairment in pulmonary function as well. In this review article, we have compiled several studies to learn how tuberculosis causes impaired lung function and further explored the long-term effects of tuberculosis on the same. We studied tuberculosis's effect on the lungs even after appropriate treatment and its relationship with obstructive and restrictive lung disorders. A significant relationship exists between chronic respiratory disorders and tuberculosis even after treatment; hence, we believe prevention is far superior to cure.

Correlation between pulmonary function and six minutes walk test with computed tomography severity score in post COVID patients

Background: The current global pandemic of the coronavirus severe acute respiratory syndrome coronavirus 2 is the world’s most critical ongoing healthcare problem, with 8.2% of critically ill patients developing acute respiratory distress syndrome and requiring Intensive care unit admission. Our study aimed to correlate CT severity score of the patient at the time of diagnosis with spirometry, 6-minute walk test and breath holding time at 12 weeks after discharge, to determine the nature of residual pulmonary dysfunction and if CT severity was a predictor of poor lung function post recovery. Methods: Ambi-directional single center study conducted in Saveetha medical college Hospital, Chennai. Patients over the age of 18 with a positive COVID-19 RTPCR report and a CTSS&gt;1 were enrolled into the study, and a sample size of 50 patients was taken after systematic random sampling. PFT, 6-minute walk test and Breath Holding Time were done at 12 weeks post discharge. Results: Mean CT severity score was: 11.48. 26% of the patients had more than 50% lung involvement on CT. There was significant negative correlation observed between FVC and Severity score (r=-0.366, p=0.009) and Breath holding and Severity score (r=-0.339, p=0.016) while there was no significant correlation between 6-minute walk test and CT Severity. Conclusions: Patients with significant lung involvement during SARS-COV-2 infection showed impaired pulmonary function test parameters in the form of a reduced FVC and breath holding time, 3 months following diagnosis. Long-term follow up and pulmonary rehabilitation is crucial to achieve respiratory recovery.

Risk factors for the deterioration of pulmonary function in primary ciliary dyskinesia.

PCD is a genetic disease leading to a decline in pulmonary function. There is only little knowledge of factors determining the long-term pulmonary outcome. Especially adherence has not been addressed yet although being an independent risk factor for an increased loss of lung capacity in other chronic respiratory diseases. Assessing the impact of bacterial airway colonization and adherence on long-term lung function in patients with PCD. Data on colonization and lung function parameters like forced expiratory volume in the first second (FEV1, Z-score) and lung clearance index (LCI2,5% ) were collected for 7.01 ± 2.2 years (893 quarters) in 44 PCD patients. Adherence was classified as good, moderate or poor. The impact of both adherence and colonization was assessed for the long-term course of FEV1, the association of colonization with lung function also quarterly. Kruskall-Wallis test, T test, ANOVA, linear regression, linear mixed model. Chronic colonization did not show any impact on the for long-term course of FEV1 , but adherence was a significant factor: patients with good adherence showed better FEV1 at the end of the observation period than children with poor adherence (-0.15 ± 0.88 vs. -2.63 ± 1.79, p < 0.01). Adherence has not yet been investigated for PCD. However, we found it to be a major significant factor affecting long-term FEV1 in PCD. Thus, it should be taken into consideration in the treatment protocols for PCD.

Impaired pulmonary function and associated factors in the elderly with tuberculosis on admission: a preliminary report

BackgroundPulmonary tuberculosis (TB) can impair pulmonary function (PF), especially in the elderly. The risk factors associated with the severity of PF impairment in the elderly with pulmonary TB remain unclear. Hence, this retrospective study aimed to address this issue to help improve the management of TB in the elderly population.MethodsFrom January 2019 to February 2022, the elderly who were admitted to our hospital for pulmonary TB and underwent PF testing were included in this analysis. The forced expiratory volume in one second percent of predicted (FEV1% predicted) and clinical characteristics were collected and analyzed retrospectively. The extent of impaired PF was then categorized based on the FEV1% predicted and classified as grade 1–5. Logistic regression analysis was used to analyze the risk factors for impaired PF.ResultsA total of 249 patients who met the enrollment criteria were included in this analysis. According to the results of FEV1% predicted, all patients were classified as grade 1 (n = 37), grade 2 (n = 46), grade 3 (n = 55), grade 4 (n = 56), or grade 5 (n = 55). Statistical analysis showed that albumin (adjusted odds ratio (aOR) = 0.928, P = 0.013), body mass index (BMI) < 18.5 kg/m2 (aOR = 4.968, P = 0.046), lesion number ≥ 3 (aOR = 4.229, P < 0.001), male (aOR = 2.252, P = 0.009), respiratory disease (aOR = 1.669, P = 0.046), and cardiovascular disease (aOR = 2.489, P = 0.027) were related to the impairment of PF.ConclusionsPF impairment is common in the elderly with pulmonary TB. The male sex, BMI < 18.5 kg/m2, lesion number ≥ 3, hypoproteinemia, and respiratory and cardiovascular comorbidities were identified as risk factors for significant PF impairment. Our findings highlight the risk factors associated with PF impairment, which may be helpful to improve the current management of pulmonary TB in the elderly to save their lung function.

Wnt3a-Loaded Extracellular Vesicles Promote Alveolar Epithelial Regeneration after Lung Injury.

Compromised regeneration resulting from the deactivation of Wnt/β-catenin signaling contributes to the progression of chronic obstructive pulmonary disease (COPD) with limited therapeutic options. Extracellular cytokine-induced Wnt-based signaling provides an alternative option for COPD treatment. However, the hydrophobic nature of Wnt proteins limits their purification and use. This study devises a strategy to deliver the membrane-bound wingless-type MMTV integration site family, member 3A (Wnt3a) over a long distance by anchoring it to the surface of extracellular vesicles (EVs). The newly engineered Wnt3aWG EVs are generated by co-expressing Wnt3a with two genes encoding the membrane protein, WLS, and an engineered glypican, GPC6ΔGPI -C1C2. The bioactivity of Wnt3aWG EVs is validated using a TOPFlash assay and a mesoderm differentiation model of human pluripotent stem cells. Wnt3aWG EVs activate Wnt signaling and promote cell growth following human alveolar epithelial cell injury. In an elastase-induced emphysema model, impaired pulmonary function and enlarged airspace are greatly restored by the intravenous delivery of Wnt3aWG EVs. Single-cell RNA sequencing-based analyses further highlight that Wnt3aWG EV-activated regenerative programs are responsible for its beneficial effects. These findings suggest that EV-based Wnt3a delivery represents a novel therapeutic strategy for lung repair and regeneration after injury.

Systematic Review of Lymphangioleiomyomatosis Outcomes in Pregnancy and a Proposed Management Guideline.

Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease that primarily affects women of reproductive age. Disease progression has been linked to estrogen exposure, and as such many patients are advised to avoid pregnancy. Data are limited regarding the interaction between LAM and pregnancy, and as such we performed a systematic review to summarize available literature reporting outcomes of pregnancies complicated by maternal LAM. This was a systematic review including randomized controlled trials, observational studies, systematic reviews, case reports, clinical practice guidelines, and quality improvement studies with full-text manuscripts or abstracts in the English language with primary data on pregnant or postpartum patients with LAM. The primary outcome was maternal outcomes during pregnancy as well as pregnancy outcomes. Secondary outcomes were neonatal outcomes and long-term maternal outcomes. This search occurred in July 2020 and included MEDLINE, Scopus, clinicaltrials.gov, Embase, and Cochrane Central. Risk of bias was ascertained using the Newcastle-Ottawa Scale. Our systematic review was registered with PROSPERO as protocol number CRD 42020191402. A total of 175 publications were identified in our initial search; ultimately 31 studies were included. Six (19%) studies were retrospective cohort studies and 25 (81%) studies were case reports. Patients diagnosed during pregnancy had worse pregnancy outcomes compared to those diagnosed with LAM prior to pregnancy. Multiple studies reported a significant risk of pneumothoraces during pregnancy. Other significant risks included preterm delivery, chylothoraces, and pulmonary function deterioration. A proposed strategy for preconception counseling and antenatal management is provided. Patients diagnosed with LAM during pregnancy generally experience worse outcomes including recurrent pneumothoraces and preterm delivery as compared to patients with a LAM diagnosis prior to pregnancy. Given that there are limited studies available, and that the majority are low-quality evidence and subject to bias, further investigation of the interaction between LAM and pregnancy is warranted to guide patient care and counseling. · Data are limited on the effects of lymphangioleiomyomatosis on pregnancy outcomes.. · We performed a systematic review to summarize pregnancy outcomes complicated by LAM.. · Patients diagnosed with LAM during pregnancy experience worse outcomes..