[Clinical phenotyping of severe Mycoplasma pneumoniae pneumonia in children].

Objective: To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods: This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children's Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results: Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions: Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

Smoking-Related Interstitial Lung Diseases.

Smoking-related interstitial lung diseases (ILDs) are a group of heterogeneous, diffuse pulmonary parenchymal disease processes associated with tobacco exposure. These disorders include pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia, acute eosinophilic pneumonia, and combined pulmonary fibrosis and emphysema. This review summarizes the current evidence of pathogenesis, clinical manifestations, diagnostic approach, prognosis, and treatment modalities for these diseases. We also discuss the interstitial lung abnormalities incidentally detected in radiologic studies and smoking-related fibrosis identified on lung biopsies.

Smoking-Related Interstitial Fibrosis (SRIF) in Patients Presenting With Diffuse Parenchymal Lung Disease.

OBJECTIVES: To describe the clinical, radiologic, and pathologic findings in cases where smoking-related interstitial fibrosis (SRIF) was diagnosed in surgical lung biopsy specimens from patients with clinical and imaging features of diffuse parenchymal lung disease (DPLD). METHODS: Cases were included in this study if patients had clinical and imaging evidence of DPLD and surgical lung biopsy specimens revealed SRIF. A dedicated multidisciplinary conference was held to correlate clinical, radiologic, and pathologic findings. RESULTS: Six cases met inclusion criteria; all six (five women/one man, aged 42-57 years, mean age 47 years) were either current smokers (five of six) or ex-smokers (one of six) and were evaluated for respiratory symptoms and abnormal pulmonary function tests, most commonly reduced forced vital capacity (n = 3) and diffusing capacity for carbon monoxide (n = 6). The most common imaging abnormalities were bilateral ground-glass opacities, which correlated with histopathologic SRIF. Follow-up of up to 10 years showed stable or improved clinical symptoms, pulmonary function tests, and radiologic findings with smoking cessation (three patients) or a decrease in smoking (three patients). No specific treatments were given, and those treated with empiric corticosteroid tapers did not show discernible responses. CONCLUSIONS: SRIF can present as clinically meaningful diffuse parenchymal lung disease in relatively young heavy smokers, characterized by bilateral ground-glass opacities and a stable clinical course.

Evaluation of the Interstitial Histological Lesions in Pulmonary Langerhans Cell Histiocytosis.

OBJECTIVE: Pulmonary Langerhans cell histiocytosis is a cystic lung disease characterized by the proliferation of parenchymal dendritic cells. The disease can become chronic or even cause pulmonary fibrosis. Our aim in this study was to investigate the typical histological findings and interstitial fibrosis in pulmonary Langerhans cell histiocytosis cases. MATERIAL AND METHOD: In the study, cases that had undergone diagnostic resection were screened. Smoking, histological stage (subacute, subacute-chronic), and cystic and eosinophilic granulomas were confirmed in the cases. In addition to emphysema, chronic nonspecific bronchiolitis, interstitial fibrosis (subpleural-paraseptal fibrosis, peribronchial fibrosis, fibrotic nonspecific interstitial pneumonia), honeycomb-type fibrocysts, and unexpected lesions were investigated. Descriptive and comparative (Fisher exact test) statistical analyses were used in the study (p < 0.05). RESULTS: A total of 27 cases were detected; age distribution was 17-68 (36.4). Smoking was present in 15 (55.5%) cases. Six (22.2%) cases were subacute, and 21 (7.7%) cases were subacute-chronic histological stage. A cystic lesion was present in 22 (81.4%) cases. All cases had emphysema accompanying the underlying lesions. Chronic nonspecific bronchiolitis was detected in 14 (51.8%) cases. Interstitial fibrosis was detected in 8 (29.6%) patients. Compared to interstitial fibrosis and nonfibrosis, there was no significant difference between being younger than 39 years, gender, smoking, and histological stage (p=0.41; 1; 0.69; 0.63, respectively). CONCLUSION: There is a risk of developing interstitial fibrosis patterns and honeycomb-type fibrocysts in the progression of pulmonary Langerhans cell histiocytosis. Histopathological evaluation can play an important role in the detection of risk groups.

Post-COVID Subacute Thyroiditis and Bronchiolitis in a Lung Transplant Recipient: A Case Report.

Lung transplant recipients are at risk for life-threatening infections including severe acute respiratory syndrome coronavirus 2-associated COVID-19. Several viral infections have been associated with the development of chronic lung allograft dysfunction. Long-term outcomes of COVID-19 on graft function are not known. A 53-year-old female patient, who underwent bilateral lung transplantation 3 years before because of stage IV sarcoidosis and secondary pulmonary hypertension was admitted in the second wave of the pandemic because of COVID-19 with symptoms including dry cough. Chest computed tomography showed ground glass opacities affecting 25% to 50% of the lung parenchyma. She was admitted to the COVID-19 Unit of our clinic. She received oxygen via nasal cannula, remdesivir, and low-dose methylprednisolone while mycofenolate acid administration was stopped. Her clinical condition improved. The first follow-up visit 1 month after the infection demonstrated deterioration in lung function. Computed tomography scan showed almost complete resolution; transbronchial biopsy was performed and proved acute allograft rejection. During the hospitalization a new onset atrial fibrillation was confirmed. In the background of atrial fibrillation and simultaneous neck pain, severe hyperthyroidism was proven. Because of thyroiditis and lung allograft rejection, high-dose steroid treatment was initiated and everolimus was added to the immunosuppressive therapy. Donor specific antibodies were also detected, hence plasmapheresis was indicated and continued with photoferesis. On the follow-up spirometry the values were stable; however, they did not reach pre-COVID levels. In lung transplant recipients COVID-19 might trigger allograft rejection in addition to virus-related thyroid disease.

Integrated relationship of nasopharyngeal airway host response and microbiome associates with bronchiolitis severity.

Bronchiolitis is a leading cause of infant hospitalizations but its immunopathology remains poorly understood. Here we present data from 244 infants hospitalized with bronchiolitis in a multicenter prospective study, assessing the host response (transcriptome), microbial composition, and microbial function (metatranscriptome) in the nasopharyngeal airway, and associate them with disease severity. We investigate individual associations with disease severity identify host response, microbial taxonomical, and microbial functional modules by network analyses. We also determine the integrated relationship of these modules with severity. Several modules are significantly associated with risks of positive pressure ventilation use, including the host-type I interferon, neutrophil/interleukin-1, T cell regulation, microbial-branched-chain amino acid metabolism, and nicotinamide adenine dinucleotide hydrogen modules. Taken together, we show complex interplays between host and microbiome, and their contribution to disease severity.

Small airways and airspace inflammation and injury distinguish lung histopathology in deployed military personnel from healthy and diseased lungs.

The link between military deployment to Southwest Asia and Afghanistan, and the risk for lung disease, including bronchiolitis, is increasingly well-recognized. However, histopathologic features that distinguish deployment-related lung diseases from other diseases affecting the small airways and airspaces are uncertain. A computer-based scoring system was developed to characterize surgical lung biopsy findings in 65 soldiers with persistent respiratory symptoms following military deployment ("deployers"). Deployer lung biopsies were compared to those from 8 patients with chronic hypersensitivity pneumonitis (cHP), 10 with smoking-related respiratory bronchiolitis, 11 with autoimmune or post-transplant obliterative bronchiolitis, and 10 normal donor lungs. Upper, middle, and lower lobe-specific findings in deployer samples were analyzed to inform optimum biopsy location choice for future patients. Surgical lung biopsies from symptomatic deployed military service members were distinguished by a combination of small airways abnormalities including smooth muscle hypertrophy (SMH), peribronchiolar metaplasia (PBM), and lymphocytic inflammation, often with constrictive/obliterative (C/O) and/or respiratory bronchiolitis (43.1%), granulomatous inflammation (38.5%), and moderate/severe emphysema (46.2%, mainly in nonsmokers). Lymphocytic pleural inflammation was common (89.2%), and vascular abnormalities occurred in nearly one-third. Histopathologic features in deployers were most strongly overlapping with cases of cHP, both showing granulomatous inflammation, PBM, and emphysema. SMH along with C/O and respiratory bronchiolitis were common in deployers but not in cHP cases. In deployers, there were significantly higher odds of small airways injury in the lower lobe compared with upper lobe samples.

Validating a bovine model for lung ultrasound of bronchiolitis.

PURPOSE: Bronchiolitis is a very common acute lung disease in infants caused commonly by respiratory syncytial virus (RSV). Point-of-care lung ultrasound is increasingly used in clinical care but proof that ultrasound reflects histological disease is lacking. Bovine calves are a good model for RSV bronchiolitis. We answered the following two questions: (1) does point-of-care lung ultrasound reflect lung pathology at the histological level in a bovine calf model of bronchiolitis? and (2) are point-of-care lung ultrasound images in human infants similar to those obtained in calves? METHODS: We experimentally infected 24 five to six-week-old bovine calves with RSV and compared six window lung ultrasound with lung histology10 days after inoculation. The calves were treated with antivirals and antipyretics leading to variable severity of illness. We used canonical discriminant analysis to determine if abnormal lung ultrasound findings reflected different histological findings. We compared the ultrasounds obtained from the calves with ultrasounds obtained from 10 human infants who were diagnosed clinically with bronchiolitis. RESULTS: Canonical discriminant analysis generally demonstrated good class separation based on the maximal severity of ultrasound finding in each acoustic window. Lung ultrasound performed poorly at detecting bronchopneumonia. Bovine ultrasounds looked similar to human infant lung ultrasounds. CONCLUSION: Point-of-care lung ultrasound abnormalities reflect lung pathology at the histological level in a bovine calf model of bronchiolitis. Point-of-care lung ultrasound images in human infants are similar to those obtained in calves.

Healthcare cost attributable to bronchiolitis: A population-based cohort study.

OBJECTIVE: To determine 1-year attributable healthcare costs of bronchiolitis. METHODS: Using a population-based matched cohort and incidence-based cost analysis approach, we identified infants <12 months old diagnosed in an emergency department (ED) or hospitalized with bronchiolitis between April 1, 2003 and March 31, 2014. We propensity-score matched infants with and without bronchiolitis on sex, age, income quintile, rurality, co-morbidities, gestational weeks, small-for-gestational-age status and pre-index healthcare cost deciles. We calculated mean attributable 1-year costs using a generalized estimating equation model and stratified costs by age, sex, income quintile, rurality, co-morbidities and prematurity. RESULTS: We identified 58,375 infants with bronchiolitis (mean age 154±95 days, 61.3% males, 4.2% with comorbidities). Total 1-year mean bronchiolitis-attributable costs were $4,313 per patient (95%CI: $4,148-4,477), with $2,847 (95%CI: $2,712-2,982) spent on hospitalizations, $610 (95%CI: $594-627) on physician services, $562 (95%CI: $556-567)] on ED visits, $259 (95%CI: $222-297) on other healthcare costs and $35 ($27-42) on drugs. Attributable bronchiolitis costs were $2,765 (95%CI: $2735-2,794) vs $111 (95%CI: $102-121) in the initial 10 days post index date, $4,695 (95%CI: $4,589-4,800) vs $910 (95%CI: $847-973) in the initial 180 days and $1,158 (95%CI: $1,104-1213) vs $639 (95%CI: $599-679) during days 181-360. Mean 1-year bronchiolitis costs were higher in infants <3 months old [$5,536 (95%CI: $5,216-5,856)], those with co-morbidities [$17,530 (95%CI: $14,683-20,377)] and with low birthweight [$5,509 (95%CI: $4,927-6,091)]. CONCLUSIONS: Compared to no bronchiolitis, bronchiolitis incurs five-time and two-time higher healthcare costs within the initial and subsequent six-months, respectively. Most expenses occur in the initial 10 days and relate to hospitalization.

Field testing two existing, standardized respiratory severity scores (LIBSS and ReSViNET) in infants presenting with acute respiratory illness to tertiary hospitals in Rwanda - a validation and inter-rater reliability study.

INTRODUCTION: There is a substantial burden of respiratory disease in infants in the sub-Saharan Africa region. Many health care providers (HCPs) that initially receive infants with respiratory distress may not be adequately skilled to differentiate between mild, moderate and severe respiratory symptoms, which may contribute to poor management and outcome. Therefore, respiratory severity scores have the potential to contributing to address this gap. OBJECTIVES: to field-test the use of two existing standardized bronchiolitis severity scores (LIBSS and ReSViNET) in a population of Rwandan infants (1-12 months) presenting with respiratory illnesses to urban, tertiary, pediatric hospitals and to assess the severity of respiratory distress in these infants and the treatments used. METHODS: A cross-sectional, validation study, was conducted in four tertiary hospitals in Rwanda. Infants presenting with difficulty in breathing were included. The LIBSS and ReSViNET scores were independently employed by nurses and residents to assess the severity of disease in each infant. RESULTS: 100 infants were recruited with a mean age of seven months. Infants presented with pneumonia (n = 51), bronchiolitis (n = 36) and other infectious respiratory illnesses (n = 13). Thirty-three infants had severe disease and survival was 94% using nurse applied LIBSS. Regarding inter-rater reliability, the intra-class correlation coefficient (ICC) for LIBSS and ReSViNET between nurses and residents was 0.985 (95% CI: 0.98-0.99) and 0.980 (0.97-0.99). The convergent validity (Pearson's correlation) between LIBSS and ReSViNET for nurses and residents was R = 0.836 (p<0.001) and R = 0.815 (p<0.001). The area under the Receiver Operator Curve (aROC) for admission to PICU or HDU was 0.956 (CI: 0.92-0.99, p<0.001) and 0.880 (CI: 0.80-0.96, p<0.001) for nurse completed LIBSS and ReSViNET respectively. CONCLUSION: LIBSS and ReSViNET were designed for infants with bronchiolitis in resource-rich settings. Both LIBSS and ReSViNET demonstrated good reliability and validity results, in this cohort of patients presenting to tertiary level hospitals. This early data demonstrate that these two scores have the potential to be used in conjunction with clinical reasoning to identify infants at increased risk of clinical deterioration and allow timely admission, treatment escalation and therefore support resource allocation in Rwanda.

Inhibition of NF-κB/IL-33/ST2 Axis Ameliorates Acute Bronchiolitis Induced by Respiratory Syncytial Virus.

BACKGROUND/AIM: Bronchiolitis is a common acute lower respiratory tract infectious disease in infants. Respiratory syncytial virus (RSV) infection is one of the main causes. Bronchiolitis can lead to a significant increase in the incidence of asthma in young children, but the mechanism of bronchiolitis transforming into asthma is still unclear. The study was aimed at investigating the role of NF-κB/IL-33/ST2 axis on RSV-induced acute bronchiolitis. METHODS: A total of 40 infants diagnosed with acute bronchiolitis infected by RSV, and 20 normal infants were included in this study. BALB/c mice (6-8 weeks old, 20 ± 1.1 g) were used as study models. Enzyme-linked immunosorbent assay (ELISA), quantitative real time PCR, western blot analysis, immunohistochemical staining, and flow cytometry analysis were performed to examine relevant indicators. RESULTS: IL-33 level was significantly elevated, and Th1/Th2 ratio is imbalance after in infants with acute bronchiolitis. In vivo study, we found that NF-κB/IL-33/ST2 axis is mediated the Th2 cytokine levels and BAL cell number induced by RSV. Acute bronchiolitis induced by RSV in a mouse model is attenuated after inhibition of NF-κB/IL-33/ST2 pathway. Moreover, we also confirmed that macrophages are important sources of IL-33 and are regulated by NF-κB pathway in RSV-induced mice. CONCLUSION: We confirmed that inhibition of NF-κB/IL-33/ST2 axis could attenuate acute bronchiolitis by RSV infected. Our findings not only demonstrate the potential role of IL-33 antibody in attenuating RSV-induced lung damage but also provide a new insight into better prevention of RSV-induced asthma by mediating NF-κB/IL-33/ST2 axis.

The role of peripheral type 2 innate lymphoid cells in bronchiolitis.

Our aim was to detect type 2 innate lymphoid cells (ILC2s)-related cytokines of infants with bronchiolitis by using Elisa, Liquidchip technology and RT-PCR and investigated its correlation with bronchiolitis. We recruited 26 infants with bronchiolitis and 20 healthy infants as control from Xiangya Hospital. Compared to the control group, the serum levels of interleukin-5 (IL-5) [41.99 (21.11) vs 25.70 (19.64)], IL-9 [27.04 (37.51) vs 8.30 (0.54)], IL-13 [184.05 (132.81) vs 121.75 (176.13)], IL-33 [83.70 (46.69) vs 11.23 (55.31)] and thymic stromal lymphopoietin (TSLP) [31.42 (5.41) vs 28.76 (2.56)] were significantly increased in infants with bronchiolitis (P < 0.05), while the level of IgE had no significant difference between the two groups [19.05 (14.15) vs 14.85 (20.2), P > 0.05]. The mRNA expression of IL-17RB (9.83 ± 0.35 vs 9.19 ± 0.58), TSLP (16.98 ± 2.12 vs 15.07 ± 2.25), retinoid acid receptor related orphan receptor α (7.18 ± 0.71 vs 5.46 ± 1.09) and trans-acting T-cell-specific transcription factor 3 (4.86 ± 0.66 vs 4.19 ± 0.90) were significantly increased in infants with bronchiolitis versus the control group (P < 0.05), while there was no statistical significance for suppression of tumorigenicity 2 (5.59 ± 0.68 vs 5.41 ± 0.87, P > 0.05). Our findings suggested that ILC2s possibly play a specific role in immunopathology of bronchiolitis.

Differential lung inflammation and injury with tobacco smoke exposure in Wistar Kyoto and spontaneously hypertensive rats.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and has been associated with periods of intense lung inflammation. The objective of this study was to characterize whether similar rat strains, possessing different genetic predispositions, might play a role in exacerbating the pathophysiology of COPD-like cellular and structural changes with progressive 12-week exposure to tobacco smoke (TS). Normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats were compared. MATERIALS AND METHODS: WKY and SH rats were exposed to filtered air or to tobacco smoke at a particulate concentration of 80 mg/m3 for 4, 8, or 12 weeks. Necropsy was performed 24 h after the last exposure to obtain cells by bronchoalveolar lavage for total cell and differential counts. Scoring of lung tissues and immunohistochemical staining for M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages were performed on paraffin-embedded lung sections. RESULTS AND DISCUSSION: With progressive exposure, TS-exposed SH rats demonstrated significant airspace enlargement, mucin production, and lung inflammation compared to their FA control and TS-matched WKY rats. Moreover, SH rats also demonstrated increased expression of the M1 marker in alveolar macrophages compared to FA control, as well as the M2 marker compared to controls and TS-exposed WKY rats. CONCLUSION: The progressive tobacco smoke exposure contributes to persistent lung injury and inflammation that can be significantly enhanced by rat strain susceptibility in the genesis of COPD.

Cryobiopsy in the diagnosis of bronchiolitis: a retrospective analysis of twenty-three consecutive patients.

Bronchiolitis manifests as a variety of histological features that explain the complex clinical profiles and imaging aspects. In the period between January 2011 and June 2015, patients with a cryobiopsy diagnosis of bronchiolitis were retrospectively retrieved from the database of our institution. Clinical profiles, imaging features and histologic diagnoses were analysed to identify the role of cryobiopsy in the diagnostic process. Twenty-three patients with a multidisciplinary diagnosis of small airway disease were retrieved (14 females, 9 males; age range 31-74 years old; mean age 54.2 years old). The final MDT diagnoses were post-infectious bronchiolitis (n = 5), constrictive bronchiolitis (n = 3), DIPNECH (n = 1), idiopathic follicular bronchiolitis (n = 3), Sjogren's disease (n = 1), GLILD (n = 1), smoking-related interstitial lung disease (n = 6), sarcoid with granulomatous bronchiolar disorder (n = 1), and subacute hypersensitivity pneumonitis (n = 2). Complications reported after the cryobiopsy procedure consisted of two cases of pneumothorax soon after the biopsy (8.7%), which were successfully managed with the insertion of a chest tube. Transbronchial cryobiopsy represents a robust and mini-invasive method in the characterization of small airway diseases, allowing a low percentage of complications and good diagnostic confidence.

Electronic cigarettes and vaping associated pulmonary illness (VAPI): A narrative review.

BACKGROUND: Electronic (e-) cigarettes are used to heat liquids producing aerosols for inhalation. Recently there have been reports of a large number of adverse outcomes relating to e-cigarette consumption (vaping), which has been referred to as "vaping associated pulmonary illness" (VAPI). AIM: This review provides an overview of clinical, radiological and pathological features of VAPI in the literature. We also describe a case of VAPI, presenting with symptoms of bronchiolitis, responding well to azithromycin in addition to the usual treatments provided for such cases. METHODS: We searched original papers, observational studies, case reports, and meta-analyses published between 2000 and 2019 in English in PubMed database using the keywords: e-cigarette, "vaping associated pulmonary illness", VAPI, EVALI, vaping AND "lung injury". We also used data of the Centers of Disease Control (CDC) website. RESULTS: From an initial search of PubMed, 62 potential articles were identified, and another 9 studies were identified from the bibliographies of retrieved articles. In this search we found 7 case series and 16 case reports, which were included in the review. In this search we also found 4 review articles. CONCLUSION: VAPI is a syndrome presenting with isolated pulmonary or combined pulmonary, gastrointestinal and constitutional symptoms and can be rapidly progressive, leading to respiratory failure, often requiring invasive respiratory support. There is an urgent need for more research on VAPI especially relating to etiology, treatment and prevention.

Differential gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model: A comprehensive transcriptome-based analysis.

BACKGROUND: Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis. METHODS: Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs). RESULTS: A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs. CONCLUSIONS: Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB.

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study.

BACKGROUND: Bronchiolitis is the leading cause of infant hospitalizations in the United States. Growing evidence supports the heterogeneity of bronchiolitis. However, little is known about the interrelationships between major respiratory viruses (and their species), host systemic metabolism, and disease pathobiology. METHODS: In an ongoing multicenter prospective cohort study, we profiled the serum metabolome in 113 infants (63 RSV-only, 21 RV-A, and 29 RV-C) hospitalized with bronchiolitis. We identified serum metabolites that are most discriminatory in the RSV-RV-A and RSV-RV-C comparisons using sparse partial least squares discriminant analysis. We then investigated the association between discriminatory metabolites with acute and chronic outcomes. RESULTS: In 113 infants with bronchiolitis, we measured 639 metabolites. Serum metabolomic profiles differed in both comparisons (Ppermutation  < 0.05). In the RSV-RV-A comparison, we identified 30 discriminatory metabolites, predominantly in lipid metabolism pathways (eg, sphingolipids and carnitines). In multivariable models, these metabolites were significantly associated with the risk of clinical outcomes (eg, tricosanoyl sphingomyelin, OR for recurrent wheezing at age of 3 years = 1.50; 95% CI: 1.05-2.15). In the RSV-RV-C comparison, the discriminatory metabolites were also primarily involved in lipid metabolism (eg, glycerophosphocholines [GPCs], 12,13-diHome). These metabolites were also significantly associated with the risk of outcomes (eg, 1-stearoyl-2-linoleoyl-GPC, OR for positive pressure ventilation use during hospitalization = 0.47; 95% CI: 0.28-0.78). CONCLUSION: Respiratory viruses and their species had distinct serum metabolomic signatures that are associated with differential risks of acute and chronic morbidities of bronchiolitis. Our findings advance research into the complex interrelations between viruses, host systemic response, and bronchiolitis pathobiology.

Interleukin 8 Association with respiratory syncytial virus bronchiolitis: a systematic review and meta-analysis.

Infants with the respiratory syncytial virus (RSV) and human rhinovirus respiratory infection (HRV) produce inflammatory interleukins (ILs) in the respiratory epithelium. The aim of this study was to evaluate the levels of interleukin-8 in RSV negative and RSV positive patients. This study search was conducted without a time limit until 2020 through the databases of PubMed, Wiley, Springer, ScienceDirect and Google Scholar search engines, by two researchers independently. The random-effects model was used to compare of interleukin-8 in RSV negative vs. RSV positive patients, using Revman software version 5 meta-analysis software. Totally, 921 patients were evaluated (207 RSV-negative and 714 RSV-positive). The mean concentration of IL8 in RSV positive patients was 15.02 pg/ml (95% CI: 13.68- 16.35%).  According to the meta-analysis results, the standardized mean difference (SMD) of IL8 concentration between RSV-positive and negative patients was 6.31 pg/ml) (95% confidence interval: 2.50- 10.13%). subtotal analysis of the IL8 laboratory assessment method revealed that there was no significant SMD deference in the studies that have used chemiluminescence (P=0.21). while IL8 concentrations were significantly higher in RSV positives in ELISA and Magnetic bead-based assays (P<0.05).  It appears that RSV positive patients may have greater levels of IL8 than RSV negative ones; whereas the synthesis of IL8 tends to be more secreted into the nasopharyngeal space; whereas the evaluation approach can also affect the results.

Bronchiolitis and Bronchiolar Disorders.

Bronchioles are noncartilaginous small airways with internal diameter of 2 mm or less, located from approximately the eighth generation of purely air conducting airways (membranous bronchioles) down to the terminal bronchioles (the smallest airways without alveoli) and respiratory bronchioles (which communicate directly with alveolar ducts and are in the range of 0.5 mm or less in diameter). Bronchiolar injury, inflammation, and fibrosis may occur in myriad disorders including connective tissue diseases, inflammatory bowel diseases, lung transplant allograft rejection, graft versus host disease in allogeneic stem cell recipients, neuroendocrine cell hyperplasia, infections, drug toxicity (e.g., penicillamine, busulfan), inhalation injury (e.g., cigarette smoke, nylon flock, mineral dusts, hard metals, Sauropus androgynous); idiopathic, common variable immunodeficiency disorder, and a host of other disorders or insults. The spectrum of bronchiolar disorders is wide, ranging from asymptomatic to fatal obliterative bronchiolitis. In this review, we discuss the salient clinical, radiographic, and histological features of these diverse bronchiolar disorders, and discuss a management approach.