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.

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.

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.

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.

Transient Tachypnea of the Newborn Is Associated With an Increased Risk of Hospitalization Due to Respiratory Syncytial Virus Bronchiolitis.

BACKGROUND: Transient tachypnea of the newborn (TTN) is a self-limiting respiratory disorder, resulting from a failure to clear the lungs of perinatal fluid. As similar pathophysiologic features are present in children with respiratory syncytial virus (RSV) bronchiolitis, we hypothesized that these two conditions may be connected. METHODS: This was a population-based cohort study that included all children born in term (≥37 weeks of gestation) without congenital malformations in Finland between 1996 and 2015. Children diagnosed with TTN (International Statistical Classification of Diseases and Related Health Problems, 10th Revision [ICD-10] code P22.1) after birth and children hospitalized because of RSV bronchiolitis (ICD-10 code J21.0) during first year of life were identified from the Medical Birth Register and National Hospital Discharge Register, respectively, and the data were linked. Logistic regression was used to analyze the association between these two conditions. RESULTS: Of the 1,042,045 children included in the study cohort, 16,327 (1.57%) were diagnosed with TTN at birth and 12,345 (1.18%) were hospitalized because of RSV bronchiolitis during the first year of life. The rate of RSV hospitalization was higher in children with a history of TTN compared with children without TTN diagnosis [260/16,327 (1.59%) vs. 12,085/1,025,718 (1.18%), respectively; P value <0.0001]. After adjusting for gestational age at birth, mode of delivery, gender, birth weight, multiple births, older siblings and maternal smoking, TTN was associated with increased risk for RSV hospitalization (odds ratio: 1.31, 95% confidence interval: 1.16-1.48). CONCLUSIONS: TTN diagnosis after birth was associated with increased risk for RSV hospitalization during the first year of life.

A Review of Smoking-Related Interstitial Fibrosis, Respiratory Bronchiolitis, and Desquamative Interstitial Pneumonia: Overlapping Histology and Confusing Terminology.

Smoking-related lung diseases traverse a spectrum of clinicopathologic entities, with cases often comprising a complex mixture of findings. The complexity of the diagnostic process extends beyond the histologic findings to the nomenclature, which is murky from a seemingly unending expansion of terms being applied to a handful of pathologic changes. Here, we focus our review on smoking-related interstitial fibrosis, respiratory bronchiolitis, and desquamative interstitial pneumonia, 3 entities that perhaps show the most histologic overlap and suffer from competing terminology.

Pulmonary cysts in smoking-related interstitial fibrosis: a form of pseudocyst secondary to pulmonary interstitial emphysema.

Smoking-related interstitial fibrosis is a distinct form of fibrosis, found in smokers, which has striking histopathological features. We present a case of pulmonary interstitial fibrosis with cysts in a 58-year-old woman who was a significant active smoker, presenting with a 7 month history of progressive dyspnea. TAC revealed thin-walled pulmonary cysts. An open lung biopsy was performed and the histopathological study showed hyaline fibrous thickening of the alveolar septa, respiratory bronchiolitis and cysts in the thickness of the interlobar septa. Immunohistochemically, the absence of an epithelial, vascular or lymphatic endothelial lining of the cysts would suggest that the cysts had been caused by pulmonary interstitial emphysema. Immunohistochemistry is essential in the differential diagnosis that includes, in this case, true cysts, pseudocysts and pulmonary lymphangiectasia.

The emerging spectrum of exposure-related bronchiolitis.

PURPOSE OF REVIEW: Exposure-related bronchiolitis is increasingly recognized as an important but challenging clinical diagnosis. Acute and chronic inhalational exposures are associated with variable clinical presentations and a spectrum of histopathologic abnormalities affecting the small airways. This review provides an overview of the histologic patterns and occupational settings for exposure-related bronchiolitis, along with recent advances in disease diagnosis and management. RECENT FINDINGS: The entire histopathologic spectrum of bronchiolitis (constrictive, obliterative, proliferative, lymphocytic, respiratory) has been reported in exposure-related bronchiolitis. Recent studies have shown that lung clearance index testing and impulse oscillometry are more sensitive than spirometry in detecting small airways abnormalities and may augment the diagnosis of occupational bronchiolitis. Prognosis in indolent occupational bronchiolitis appears more favorable than some other types of bronchiolitis but is variable depending on the extent of bronchiolar inflammation and the stage of disease at which exposure removal occurs. SUMMARY: No specific histopathologic pattern of bronchiolitis is pathognomonic for occupational bronchiolitis as one or more histologic patterns may be present. A high index of suspicion is needed for exposure and disease recognition. Recent advances that may aid in diagnosis include transbronchial cryobiopsy, lung clearance index testing, and impulse oscillometry, although further research is needed.

Respiratory syncytial virus in Brazilian infants - Ten years, two cohorts.

BACKGROUND: Each year, a considerable amount of children will experience at least one episode of acute viral bronchiolitis (AVB) during their first year of life. About 10% of them will be hospitalized, with significant physical and economic burdens. OBJECTIVES: To compare two cohorts of infants with AVB, from same region, in a ten-year interval, regarding epidemiologic factors and viral etiology. STUDY DESIGN: Cohorts: 142 (2004) and 172 (2014) infants at ages zero to 12 months; clinical diagnosis of AVB; medical care in hospital and genetic screening of nasopharyngeal secretion for respiratory viruses. RESULTS: The comparative analysis showed a difference in the percentage of respiratory syncytial virus (RSV) positive patients [2004 (33.1%); 2014 (70.3%)] (p<0.01). No differences were noted regarding gender, breastfeeding, tobacco exposure, crowding and maternal education. There was a difference as to the month of incidence (seasonality) of AVB (higher in April 2014). There was a higher age at attendance in the first cohort, and lower birth weight and gestational age ratios in the second cohort (p<0.05). There were no differences in hospitalization time, need of mechanical ventilation and number of deaths, however a difference regarding co-morbidities was noted (higher in 2004) (p<0.001). CONCLUSION: None of the analyzed variables had an impact on severity features. Virology and immunology must be considered in this kind of situation, by studying genetic variants and the maturation of the immune system in AVB by RSV or other viruses.

Follicular bronchiolitis in an HIV-infected individual on combination antiretroviral therapy with low CD4+ cell count but sustained viral suppression.

A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis and was treated with prednisolone. Despite complete viral suppression and increasing CD4+ count (162 cells/µL), he was readmitted with PCP in April 2015. Subsequently, he returned to Denmark (CD4+ count: 80 cells/µL, viral suppression). Over the following months, he developed progressive dyspnoea. Lung function tests demonstrated severely reduced lung capacity with an obstructive pattern and a moderately reduced diffusion capacity. High resolution computer tomography revealed minor areas with tree-in-bud pattern and no signs of air trapping on expiratory views. Lung biopsy showed lymphocytic infiltration surrounding the bronchioles with sparing of the alveolar septa. He was diagnosed with follicular bronchiolitis. The patient spontaneously recovered along with an improvement of the immune system.

The Changes of Th17/Treg and Related Cytokines: IL-17, IL-23, IL-10, and TGF-ß in Respiratory Syncytial Virus Bronchiolitis Rat Model.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization that lead to high morbidity and mortality among young infants. T helper 17 (Th17) cells and regulatory T cells (Tregs) play essential roles in the pathogenesis of autoimmune, cancer, and inflammatory diseases. However, whether changes in T-cell subsets are related to the systemic immune responses in RSV-caused bronchiolitis merit further investigation. Three-week-old Sprague Dawley (SD) rats were randomly divided into the normal control (NC) and RSV bronchiolitis (RSV-B) groups. An RSV-B model was successfully established using nasal drip containing RSV. Furthermore, pathological changes in the lung tissues were observed using hematoxylin and eosin staining. Flow cytometry determined the levels of Th17 and Treg subsets. The related cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of related transcription factors, such as RORγt and FOXP3, were examined using real-time quantitative PCR and western blot analysis. The RSV-B group exhibited pulmonary interstitial hyperemia and edema, inflammatory cell infiltration, wide alveolar septa, and bronchial collapse and deformation. The percentage of Th17 cells in RSV-B group was about 2.3 fold higher than that of NC group, and the concentration of IL-17, IL-23 and RORγt was higher than in NC group. In contrast, the percentage of Treg cells in the RSV-B group was approximately 0.7 fold lower than that in the NC group, and the levels of IL-10, TGF-ß, and FOXP3 in the RSV-B group were lower than those in the NC group. The above results were statistically significant. The changes of Th17/Treg, and their associated cytokines, specific transcription factors, are present in RSV bronchiolitis model rats, which may play an important role in the pathogenesis of RSV bronchiolitis.

MicroRNA-218 acts by repressing TNFR1-mediated activation of NF-κB, which is involved in MUC5AC hyper-production and inflammation in smoking-induced bronchiolitis of COPD.

Dysregulation of microRNAs (miRNAs) has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD), which is largely attributable to cigarette smoke (CS). However, little is known about the effect of miRNAs on CS-induced mucus hypersecretion and the inflammatory response in the airway epithelium, which are pathological characteristics of COPD-related chronic bronchiolitis. As determined in the present investigation, population-based data indicate that smokers with COPD had serious airflow obstruction and inflammation, whereas smokers without COPD had mild airflow obstruction and inflammation. Moreover, levels of serum miR-218 positively correlated with FEV1/FVC% and negatively correlated with levels of serum IL-6 and IL-8. In human bronchial epithelial (HBE) cells, cigarette smoke extract (CSE) decreased miR-218 levels and increased levels of MUC5AC, interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor receptor 1 (TNFR1), and p-p65. Enhancement of miR-218 levels by an miR-218 mimic blocked these CSE-induced changes. Moreover, luciferase reporter assays confirmed that miR-218 bound to the 3'UTR region of TNFR1 mRNA. Down-regulation of TNFR1 blocked the CSE-induced increases of MUC5AC, IL-6, and IL-8 and the activation of NF-κB. Furthermore, over-expression of miR-218 attenuated the CSE-induced overproduction of MUC5AC, IL-6, and IL-8, effects that were reversed by elevated expression of TNFR1. In sum, our findings provide a mechanism by which miR-218 regulates CSE-induced MUC5AC hyper-production and inflammation by targeting TNFR1-mediated activation of NF-κB, indicating that overexpression of miR-218 may be a strategy against cigarette smoking-induced bronchiolitis in COPD.

HRCT findings of childhood follicular bronchiolitis.

BACKGROUND: Follicular bronchiolitis is a lymphoproliferative form of interstitial lung disease (ILD) defined by the presence of peribronchial lymphoid follicles. Follicular bronchiolitis has been associated with viral infection, autoimmune disease and immunodeficiency. The most common clinical manifestation is respiratory distress in infancy followed by a prolonged course with gradual improvement. We found no reports of systematic review of high-resolution computed tomography (HRCT) findings in pediatric follicular bronchiolitis. OBJECTIVE: The purpose of this study was to describe the HRCT findings of follicular bronchiolitis in children and correlate these imaging findings with histopathology. MATERIALS AND METHODS: A 5-year retrospective review of all pathology-proven cases of follicular bronchiolitis was performed. Inclusion criteria were age <18 years and an HRCT within 6 months of lung biopsy. HRCTs were reviewed by three observers and scored using the system previously described by Brody et al. RESULTS: Six patients met the inclusion criteria with age range at HRCT of 7-82 months (median: 39.5 months). Pulmonary nodules (n=6) were the most common HRCT finding followed by focal consolidation (n=5), bronchiectasis (n=4) and lymphadenopathy (n=3). Tree and bud opacities and nodules on CT correlated with interstitial lymphocytic infiltrates and discrete lymphoid follicles on pathology. CONCLUSION: The salient HRCT findings of childhood follicular bronchiolitis are bilateral, lower lung zone predominant pulmonary nodules and bronchiectasis with infantile onset of symptoms. These characteristic HRCT findings help differentiate follicular bronchiolitis from other forms of infantile onset ILD.