Bio-Inspired Screwed Conduits from the Microfluidic Rope-Coiling Effect for Microvessels and Bronchioles

Tubular microfibers have recently attracted extensive interest for applications in tissue engineering.However,the fabrication of tubular fibers with intricate hierarchical structures remains a major challenge.Here,we present a novel one-step microfluidic spinning method to generate bio-inspired screwed conduits(BSCs).Based on the microfluidic rope-coiling effect,a viscous hydrogel precursor is first curved into a helix stream in the channel,and then consecutively packed as a hollow structured stream and gelated into a screwed conduit(SC)via ionic and covalent crosslinking.By taking advantage of the excellent fluid-controlling ability of microfluidics,various tubes with diverse structures are fabricated via simple control over fluid velocities and multiple microfluidic device designs.The perfusability and permeability results,as well as the encapsulation and culture of human umbilical vein endothelial cells(HUVECs),human pulmonary alveolar epithelial cells(HPAs),and myogenic cells(C2C12),demonstrate that these SCs have good perfusability and permeability and the ability to induce the formation of functional biostructures.These features support the uniqueness and potential applications of these BSCs as biomimetic blood vessels and bronchiole tissues in combination with tissue microstructures,with likely application possibilities in biomedical engineering.

Effect of Gas Oscillation-Induced Irreversible Flow in Transitional Bronchioles of Human Lung

Gas exchange in human lungs is established by several flow mechanisms. In the present study, the features of gas displacement in the distal bronchioles of a human lung are investigated by both numerical calculation and experimental observation with particle image velocimetry. The effect of respiration frequency is considered, such as high frequency oscillatory ventilation. By comparing the obtained results, it has been found that the redistribution of gas is attributed to irreversible flow, which is remarkable in higher frequencies oscillation with even lower tidal volumes. Owing to the continuous driving, a time-averaged net flow was induced and intensified by the oscillation. Thus, the gas in the centre region penetrated the deeper region and the outer gas was evacuated to the upper region. Consequently, this streaming contributes to prompt gas replacement. Furthermore, we analysed the effect of the respiration wave form to consider the flow acceleration. From this inspection, it was found that the enhanced inertial force tends to encourage the irreversible flow.

大环内酯类抗生素治疗慢性气道炎症性疾病的疗效与不良反应

大环内酯类抗生素（macrolides,MA）已被用于临床治疗慢性气道炎症性疾病,包括弥漫性泛细支气管炎（diffuse panbronchiolitis,DPB）、囊性纤维化（cystic fibrosis,CF）、非囊性纤维化的支气管扩张（non-cystic fibrosis bronchiectasis,NCFB）、哮喘、慢性阻塞性肺部疾病（chronic obstructive pulmonary disease,COPD）、闭塞性细支气管炎（bronchiolitis obliterans，BO）等。

Streaming Caused by Oscillatory Flow in Peripheral Airways of Human Lung

Oscillatory flow facilitates gas exchange in human respiration system. In the present study, both numerical calculation and PIV (Particle Image Velocimetry) measurement indicate that, under the application of HFOV (High Frequency Oscillatory Ventilation), apparent steady streaming is caused and augmented in distal airways by the continuous oscillation, i.e., the core air moves downwards and the peripheral air evacuates upwards within bronchioles. The net flow of steady streaming serves to overcome the lack of tidal volume in HFOV and delivers fresh air into deeper lung region. Also, numerical calculations reveal that the intensity of steady streaming is mainly influenced by the geometry of airways with provided oscillatory frequency and tidal volume, and it rises with Re and Wo up to a Re of about 124 and Wo of about 5. Steady streaming is considered as an important factor for the ventilation efficiency of HFOV.

儿童闭塞性细支气管炎30例临床分析

闭塞性细支气管炎（bronchiolitis obliterans,BO）是一种较少见的儿童慢性阻塞性肺部疾病,下呼吸道的严重损伤后导致不同程度的炎症反应和瘢痕形成,最终导致细支气管的狭窄和（或）完全闭塞。在儿童中,最常见的原因是感染后闭塞性细支气管炎（post-infections bronchiolitis obliterans,PIBO）,部分与结缔组织疾病、吸入有毒物质、骨髓/器官移植等有关。

多层螺旋CT在儿童闭塞性细支气管炎中的诊断价值

闭塞性细支气管炎（bronchiolitis obliterans）是一种由小气道损伤后炎症及纤维化病变引起的慢性气流阻塞性疾病-（[1]）。由于本病较少和严重,儿科及影像科医生对该病的认识不足,延误治疗,影响预后。近年来,随着多层螺旋CT的广泛应用,该病的诊断率已有所提高。笔者回顾性分析本院近2年诊断为闭塞性细支气管炎患儿的临床及CT表现,现报告如下,旨在提高对本病的认识及诊断水平。

Patterns of airway involvement in inflammatory bowel diseases

Extraintestinal manifestations occur commonly in inflammatory bowel diseases(IBD). Pulmonary manifestations(PM) of IBD may be divided in airway disorders, interstitial lung disorders, serositis, pulmonary vasculitis, necrobiotic nodules, drug-induced lung disease, thromboembolic lung disease and enteropulmonary fistulas. Pulmonary involvement may often be asymptomatic and detected solely on the basis of abnormal screening tests. The common embryonic origin of the intestine and the lungs from the primitive foregut, the co-existence of mucosa associated lymphoid tissue in both organs, autoimmunity, smoking and bacterial translocation from the colon to the lungs may all be involved in the pathogenesis of PM in IBD. PM are mainly detected by pulmonary function tests and highresolution computed tomography. This review will focus on the involvement of the airways in the context of IBD, especially stenoses of the large airways, tracheo-bronchitis, bronchiectasis, bronchitis, mucoid impaction, bronchial granulomas, bronchiolitis, bronchiolitis obliterans syndrome and the co-existence of IBD with asthma, chronic obstructive pulmonary disease, sarcoidosis and a1-antitrypsin deficiency.

Role of gastroesophageal reflux disease in lung transplantation

Lung transplantation is one of the highest risk solid organ transplant modalities. Recent studies have demonstrated a relationship between gastroesophageal reflux disease(GERD) and lung transplant outcomes, including acute and chronic rejection. The aim of this review is to discuss the pathophysiology, evaluation, and management of GERD in lung transplantation, as informed by the most recent publications in the field. The pathophysiology of reflux-induced lung injury includes the effects of aspiration and local immunomodulation in the development of pulmonary decline and histologic rejection, as reflective of allograft injury. Modalities of reflux and esophageal assessment, including ambulatory p H testing, impedance, and esophageal manometry, are discussed, as well as timing of these evaluations relative to transplantation. Finally, antireflux treatments are reviewed, including medical acid suppression and surgical fundoplication, as well as the safety, efficacy, and timing of such treatments relative to transplantation. Our review of the data supports an association between GERD and allograft injury, encouraging a strategy of early diagnosis and aggressive reflux management in lung transplant recipients to improve transplant outcomes. Further studies are needed to explore additional objective measures of reflux and aspiration, better compare medical and surgical antireflux treatment options, extend followup times to capture longer-term clinical outcomes, and investigate newer interventions including minimally invasive surgery and advanced endoscopic techniques.

Significance of platelet count in children admitted with bronchiolitis

AIM To determine the true prevalence of thrombocytosis in children less than 2 years of age with bronchiolitis,its association with risk factors,disease severity and thromboembolic complications.METHODS A retrospective observational medical chart review of 305 infants aged two years or less hospitalized for bronchiolitis.Clinical outcomes included disease severity,duration of hospital stay,admission to pediatric intensive care unit,or death.They also included complications of thrombocytosis,including thromboembolic complications such as cerebrovascular accident,acute coronary syndrome,deep venous thrombosis,pulmonary embolus,mesenteric thrombosis and arterial thrombosis and also hemorrhagic complications such as bleeding(spontaneous hemorrhage in the skin,mucous membranes,gastrointestinal,respiratory,or genitourinary tracts).RESULTS The median age was 4.7 mo and 179 were males(59%).Respiratory syncytial virus was isolated in 268(84%),adenovirus in 23(7%) and influenza virus A or B in 13(4%).Thrombocytosis(platelet count > 500 × 109/L) occurred in 88(29%;95%CI:24%-34%),more commonly in younger infants with the platelet count declining with age.There was no significant association with the duration of illness,temperature on admission,white blood cell count,serum C-reactive protein concentration,length of hospital stay or admission to the intensive care unit.No death,thrombotic or hemorrhagic events occurred.CONCLUSION Thrombocytosis is common in children under two years of age admitted with bronchiolitis.It is not associated with disease severity or thromboembolic complications.

Cryptogenic organizing pneumonia associated with pregnancy:A case report

BACKGROUND Cryptogenic organizing pneumonia(COP),formerly known as bronchiolitis obliterans organizing pneumonia,is an extremely rare disease in pregnancy.In this case,we report on COP diagnosed in recurrent pneumonia that does not respond to antibiotics in pregnant woman.CASE SUMMARY A 35-year-old woman with no prior lung disease presented with concerns of chest pain with cough,sputum,dyspnea,and mild fever at 11 wk’gestation.She was diagnosed with community-acquired pneumonia and treated with antibiotics;her symptoms improved temporarily.Four weeks after discharge,she was readmitted with aggravated symptoms.Chest computed tomography demonstrated multifocal patchy airspace consolidation and ground-glass opacities at the basal segments of the right lower lobe,at the lateral basal segment of the lower lobe,and at the lingular segment of the left upper lobe.Bronchoalveolar lavage revealed an increased lymphocyte count and a decreased CD4/CD8 ratio.Prednisolone(0.5 mg/kg/d)was administered for 10 d after the second admission.Dyspnea improved after 3 d of steroid treatment and other symptoms improved on the 5th day of steroid administration.Post-delivery transbronchial lung biopsy further revealed the presence of granulation tissue with fibroblasts in smallbronchiole lumens.CONCLUSION This case suggests that it is important to differentiate COP from atypical pneumonia in the deteriorated condition despite antibiotic treatment.

Atypical respiratory complications of dengue fever

In last decade,dengue has emerged as one of the most important vector born disease.With increasing cases,uncommon presentations and complications are now commonly recognized.Here,we report two cases of rare pattern of respiratory involvement in dengue:acute respiratory distress syndrome and bronchiolitis with respiratory failure.

Clinical analysis of 114 cases of bronchiolitis in infants

BACKGROUND Bronchiolitis is a common lower respiratory tract infection in infants and young children.Severe cases may be accompanied by obvious dyspnea and oxygen saturation decline.AIM To summarize the clinical features,standard diagnosis,and treatment of bronchi-olitis.METHODS This is a retrospective analysis of 114 pediatric patients(74 males,40 females)who were first diagnosed as having bronchioles at the Department of Pediatrics of Tongling Maternal and Child Health Hospital from January 2019 to December 2019.The clinical features,imaging features,treatment,and other clinical data were recorded and analyzed.RESULTS The age of onset of the disease was mainly from 1 mo to 6 mo(75.4%),and the time to hospital visit was mostly from the 2nd day to the 4th day of the course of the disease(75.4%).Lung imaging examination showed increase in lung texture,fuzzy(93.8%).The main treatment was atomization therapy:Budesonide combined with terbutaline(45.6%)and budesonide combined with salbutamol(38.5%).The average hospitalization time was 7.1±2.4 d,and the overall cure rate was 94.7%.In patients without bacterial infection,the use of antibiotics significantly prolonged the length of hospital stay(7.8±2.5 d vs 5.7±1.8 d)and improved the cure rate(98.3%vs 87.9%,P<0.05).CONCLUSION Infants with bronchiolitis are mainly male and tend to have a good prognosis.However,the unneeded use of antibiotics may prolong the length of hospital stay significantly,which imposes the burden both on the patients and hospital system.CONCLUSION Bronchiolitis is a common acute respiratory infectious disease in infants and young children.It mainly affects male children and the age onset is between 1 to 6 mo.The standard use of antibiotics should be emphasized in view of the prolonged average length of hospital stay between the antibiotic treatment group and the non-antibiotic treatment group.When the course of disease is more than 7 d or the treatment effect is poor,active anti-infective treatment is needed to improve the long-term prognosis.Very few children have recurrent cough and wheezing symptoms within 1 year,which may be related to the risk of later asthma attack.FOOTNOTES Author contributions:Shi C and Wu MH contributed to study conception and design,and provision of study materials or patients;Shi C contributed to administrative support;Zuo A,Yang MM,and Jiang RR contributed to data collection and assembly;Shi C contributed to data analysis and interpretation,and manuscript writing;all authors contributed to the final approval of the manuscript.Institutional review board statement:The study was conducted in accordance with the Declaration of Helsinki(as revised in 2013).The study was approved by Institutional Review Board of Tongling Maternal and Child Health Hospital.

Application of Xiao’er Kechuanling Oral Liquid Combined with Tulobuterol Patch in Children with Bronchiolitis

[Objectives]To explore the use of Xiao’er Kechuanling Oral Liquid combined with Tulobuterol Patch on the basis of comprehensive treatment,compare it with the combined aerosol inhalation of terbutaline,ipratropium bromide and budesonide which are commonly used in clinic,and observe the curative effect in the treatment of acute bronchiolitis and the effect on serum IL-4 and IL-8.[Methods]80 children with acute bronchiolitis were randomly divided into observation group(n=40)and control group(n=40),and both groups were given routine comprehensive treatment.The observation group was treated with Xiao’er Kechuanling Oral Liquid combined with Tulobuterol Patch and budesonide,while the control group was treated with combined aerosol inhalation of terbutaline,ipratropium bromide and budesonide.The curative effect of the two groups was observed;the remission duration of cough,wheezing,dyspnea and nocturnal wheezing,and the disappearance time of wheezing rales and moist rales were observed in the two groups;the treatment course of intravenous infusion of methylprednisolone sodium succinate,oxygen inhalation time,sputum suction times and hospitalization time were observed in the two groups;the changes of serum IL-4 and IL-8 were observed before and after treatment in the two groups;the adverse drug reactions were observed.[Results](i)The total effective rate of the two groups was 100%(P>0.05),but the cure rate of the observation group(72.5%)was significantly higher than that of the control group(42.5%)(P<0.01).(ii)The disappearance time of cough,wheezing rales and moist rales and hospitalization time in the observation group were significantly shorter than those in the control group(P<0.01),the remission duration of nocturnal wheezing in the observation group was shorter than that in the control group(P<0.05),and the remission duration of wheezing and dyspnea in the control group was slightly longer than that in the control group(P>0.05).(iii)There was no significant difference(P>0.05)in serum IL-4 and serum IL-8 between the two groups before and after treatment.After treatment,the levels of serum IL-4 and IL-8 in the observation group and the control group were significantly lower than those before treatment in the observation group and the control group.[Conclusions]On the basis of comprehensive treatment,the use of Xiao’er Kechuanling Oral Liquid combined with Tulobuterol Patch in the treatment of acute bronchiolitis could reduce the effect of nocturnal wheezing on sleep,reduce the levels of serum IL-4 and IL-8,and significantly improve adverse symptoms.

Association of breastfeeding with tidal breathing analysis in infants with bronchiolitis

BACKGROUND Tidal breathing flow-volume(TBFV)analysis provides important information about lung mechanics in infants.AIM To assess the effects of breastfeeding on the TBFV measurements of infants who recover from acute bronchiolitis.METHODS In this cross-sectional study,TBFV analysis was performed in infants with bronchiolitis prior to hospital discharge.The ratio of time to peak expiratory flow to total expiratory time(tPEF/tE)at baseline and after the administration of 400 mcg salbutamol was evaluated.RESULTS A total of 56 infants(35 boys),aged 7.4±2.8 mo,were included.Of them,12.5%were exposed to tobacco smoke and 41.1%were breastfed less than 2 mo.There were no differences in baseline TBFV measurements between the breastfeeding groups;however,those who breastfed longer than 2 mo had a greater change in tPEF/tE after bronchodilation(12%±10.4%vs 0.9%±7.1%;P<0.001).Moreover,there was a clear dose-response relationship between tPEF/tE reversibility and duration of breastfeeding(P<0.001).In multivariate regression analysis,infants who breastfed less(regression coefficient-0.335,P=0.010)or were exposed to cigarette smoke(regression coefficient 0.353,P=0.007)showed a greater change in tPEF/tE after bronchodilation,independent of sex,prematurity,and family history of asthma or atopy.CONCLUSION Infants who recover from bronchiolitis and have a shorter duration of breastfeeding or are exposed to cigarette smoke,have TBFV measurements indicative of obstructive lung disease.

From bronchiolitis guideline to practice: A critical care perspective

Acute viral bronchiolitis is a leading cause of admission to pediatric intensive care units, but research on the care of these critically ill infants has been limited. Pathology of viral bronchiolitis revealed respiratory obstruction due to intraluminal debris and edema of the airways and vasculature. This and clinical evidence suggest that airway clearance interventions such as hypertonic saline nebulizers and pulmonary toilet devices may be of benefit, particularly in situations of atelectasis associated with bronchiolitis. Research to distinguish an underlying asthma predisposition in wheezing infants with viral bronchiolitis may one day lead to guidance on when to trial bronchodilator therapy. Considering the paucity of critical care research in pediatric viral bronchiolitis, intensive care practitioners must substantially rely on individualization of therapies based on bedside clinical assessments. However, with the introduction of new diagnostic and respiratory technologies, our ability to support critically ill infants with acute viral bronchiolitis will continue to advance.

Chronic lung allograft dysfunction post-lung transplantation:The era of bronchiolitis obliterans syndrome and restrictive allograft syndrome

Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment of treatment.The consensus statement from the International Society for Heart and Lung Transplantation on CLAD in 2019 classified CLAD into two main phenotypes:Bronchiolitis obliterans syndrome and restrictive allograft syndrome.Along with this clear classification,further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are desired.In this review,we summarize the new definition of CLAD and update and summarize the existing knowledge on the underlying mechanisms of bronchiolitis obliterans syndrome and restrictive allograft syndrome,which have been elucidated from clinicopathological observations and animal experiments worldwide.

Child Acute Lower Respiratory Tract Infection in Pediatrics Intensive Care Unit at University Hospital of Brazzaville (Congo)

In order to contribute to reduction of morbidity and mortality due to low acute respiratory infections in pediatrics, the objective of this study was to determine the epidemiological profile and to identify the factors favoring and those associated with the risk of deceased. We reviewed the cases of children aged between 1 and 59 months hospitalized between January and December 2015 in the pediatric intensive care unit of the CHU of Brazzaville and retained those whose diagnosis of discharge was an ALRI. The study variables were: epidemiological, clinical, paraclinic, diagnostic, therapeutic and evolutionary. For 2012 hospitalized children, 400 (19.8%) were hospitalized for an ALRI. There were 235 boys (58.8%) and 165 girls (41.2%) of average age. Infants aged 1 to 11 months were the most affected n = 260 (65%). They were insufficiently immunized with haemophilus influenza B and pneumococcus n = 378 (94.5%);Fully immunized n = 20 (5%), the average delay for consultation after the first symptom was 5.03 ± 3.86 days;Denutrition was rated n = 180 (45%), positive retroviral serology n = 19 cases (4.8%). The main nosological varieties were: bronchiolitis n = 223 (55.7%), pneumonia n = 145 (36.2%). One death was rated n = 65 (16.3%). The mortality determinants were: prematurity, vaccination status and HIV/AIDS infection. The frequency and severity of ALRIs necessitates a strengthened program of integrated management of childhood illnesses, and public health actions targeting the factors that promote and contribute to the risk of death.

Cytokine responses in infants infected with respiratory syncytial virus

Introduction: Variability in severity of Respiratory Syncytial Virus (RSV) infection is reportedly due to differences in inflammatory response. Objective: To characterize the cytokine response in RSV+ infants aged 0 - 36 months and to relate their responses to disease severity. Methods: Nasopharyngeal aspirations (NPAs) were analyzed for RSV and IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-1RA, IL-4R, IFN-γ, sTNFR1, sTNFR2, and TNF-α. Clinical data were collected from the medical records. Results: We included 331 infants of whom 214 were RSV+. In comparison to RSV- infants, they had significantly higher levels of TNF-α, IL-6, IL-1β, and IFN-γ (p α, IL-6, and IL-1β. sTNFR1/2 were significantly increased in RSV+ infants. Hospitalized patients had significantly higher levels of TNF-α, sTNFR2, and IL-10 (p < 0.05) than non-hospitalized patients. The cytokine response could not be related to disease severity. We found no evidence of a skewed Th1/Th2 immune profile. Conclusion: In acute RSV disease, infected infants’ NPAs contain a significant amount of pro-inflammatory cytokines. Whether this response is beneficial or deleterious remains unanswered. Interpersonal variations in cytokine responses might be linked to an inherited tendency to variations in disease severity.

RELATIONSHIP BETWEEN HYPERSENSITIVITY TYPE I AND WHEEZING BY RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTION

We studied the RSV specific IgE antibody, histamine and basophil from infants with RSV bronchiolitis and found during the acute phase either the titers of RSV-IgE or the concentration of histamine increased significantly, the number of basophil and basophil degranulation in the presence of RSV antigen also increased. In vitro studies revealed hypersensitivity participates in the pathogenesis of RSV bronchiolitis. We also found that infants with RSV bronchiolitis, the RSV-IgE persisted for a long time presumably this plays an important role in recurrent wheezing after RSV infection for years.

Use of flow cytometry to investigate the cytokine response pattern in infants with respiratory syncytial virus infection and bronchiolitis

Objective: To investigate the cytokine response pattern (IL 4/IFN γ ) in infants with RSV infections and bronchiolitis during the acute phase. Methods: Four color flow cytometry was used to measure intracellular IL 4 and IFN γ expressions in peripheral blood CD3+ and CD8+ lymphocytes from RSV infected and bronchiolitis infants. Serum IL 4 and IFN γ levels were also determined. Results: RSV infected and bronchiolitis infants showed no statistical differences from not RSV infected or pneumonia infants and control in the frequency of IL 4 and IFN γ expressions in CD3+CD8 lymphocytes, showed no obvious Th1/Th2 imbalance, while IFN γ was expressed much more frequently in CD3+CD8+ lymphocytes. Systematically, RSV infected and bronchiolitis infants showed much lower levels of serum IL 4 and IL 4/IFN γ ratios and much higher serum IFN γ levels than control. However, there were no statistical differences in the above three indices between RSV infected and not RSV infected infants or between bronchiolitis and pneumonia infants, except that bronchiolitis infants had a higher level of serum IFN γ than pneumonia infants statistically. Conclusions: There is no type 2 cytokine response predominance in the acute phase of RSV infection and bronchiolitis. IL 4 production is suppressed and IFN γ production upregulated, the latter being most prominent in bronchiolitis infants.