Bronchiolitis and Bronchiolar Disorders

2020 ◽  
Vol 41 (02) ◽  
pp. 311-332
Author(s):  
Claudia Ravaglia ◽  
Venerino Poletti
Keyword(s):  
Connective Tissue Diseases ◽  
Inhalation Injury ◽  
Management Approach ◽  
Internal Diameter ◽  
Small Airways ◽  
Cell Hyperplasia ◽  
Immunodeficiency Disorder ◽  
Bowel Diseases ◽  
Mineral Dusts ◽  
Conducting Airways

AbstractBronchioles 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.

Pathology of Small Airways Disease

2010 ◽  
Vol 134 (5) ◽  
pp. 702-718 ◽  
Author(s):  
Timothy Craig Allen
Keyword(s):  
Lung Diseases ◽  
Vascular Diseases ◽  
Lung Parenchyma ◽  
Small Airways ◽  
Diagnostic Features ◽  
Cell Hyperplasia ◽  
Collagen Vascular Diseases ◽  
Diffuse Panbronchiolitis ◽  
Mineral Dusts ◽  
Inflammatory Bowel

Abstract Context.—The term small airways disease encompasses a generally poorly understood group of lung diseases that may arise primarily within the small airways or secondarily from diseases primarily affecting the bronchi or lung parenchyma. Their histology may be confusing; however, because treatments and prognoses vary, correct pathologic diagnosis is important. Objective.—To present a nonexhaustive review of the pathology of primary and secondary small airways diseases, including small airways disease related to tobacco; to various other exposures, including mineral dusts; to diseases involving other areas of the lung with secondary bronchiolar involvement; and to recently described bronchiolitic disorders. Data sources.—Current literature is reviewed. Conclusions.—Small airways diseases include a wide variety of diseases of which the pathologist must consider. Uncommon conditions such as diffuse idiopathic neuroendocrine cell hyperplasia and diffuse panbronchiolitis may show relatively specific diagnostic features histologically; however, most small airways diseases exhibit nonspecific histologic features. Conditions not considered primary pulmonary diseases, such as collagen vascular diseases, bone marrow transplantation, and inflammatory bowel disease, must also be considered in patients with small airways changes histologically. Clinical and radiologic correlation is important for obtaining the best possible diagnosis.

Altered allergen-induced eosinophil trafficking and physiological dysfunction in airways with preexisting virus-induced injury

2007 ◽  
Vol 292 (1) ◽  
pp. L85-L91 ◽  
Author(s):  
Ronald L. Sorkness ◽  
Kathryn M. Herricks ◽  
Renee J. Szakaly ◽  
Robert F. Lemanske ◽  
Louis A. Rosenthal
Keyword(s):  
Bronchoalveolar Lavage ◽  
Allergen Challenge ◽  
Allergen Exposure ◽  
Lung Mechanics ◽  
Lower Airway ◽  
Small Airways ◽  
Airway Wall ◽  
Cell Hyperplasia ◽  
Airway Pathology ◽  
Air Space

Although both asthmatics and allergic rhinitics develop an acute inflammatory response to lower airway allergen challenge, only asthmatics experience airway obstruction resulting from chronic environmental allergen exposure. Hypothesizing that asthmatic airways have an altered response to chronic allergic inflammation, we compared the effects of repeated low-level exposures to inhaled Alternaria extract in sensitized rats with preexisting chronic postbronchiolitis airway dysfunction versus sensitized controls with normal airways. Measurements of air space (bronchoalveolar lavage) inflammatory cells, airway goblet cells, airway wall collagen, airway wall eosinophils, airway alveolar attachments, and pulmonary physiology were conducted after six weekly exposures to aerosolized saline or Alternaria extract. Postbronchiolitis rats, but not those starting with normal airways, had persistent increases in airway wall eosinophils, goblet cell hyperplasia in small airways, and loss of lung elastic recoil after repeated exposure to aerosolized Alternaria extract. Despite having elevated airway wall eosinophils, the postbronchiolitis rats had no eosinophils in bronchoalveolar lavage at 5 days after the last allergen exposure, suggesting altered egression of tissue eosinophils into the air space. In conclusion, rats with preexisting airway pathology had altered eosinophil trafficking and allergen-induced changes in airway epithelium and lung mechanics that were absent in sensitized control rats that had normal airways before the allergen exposures.

Sites of allergic airway smooth muscle remodeling and hyperresponsiveness are not associated in the rat

2010 ◽  
Vol 109 (4) ◽  
pp. 1170-1178 ◽  
Author(s):  
Sana Siddiqui ◽  
Taisuke Jo ◽  
Meiyo Tamaoka ◽  
Karim H. Shalaby ◽  
Heberto Ghezzo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Goblet Cell ◽  
Allergen Challenge ◽  
Brown Norway ◽  
Small Airways ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Wall Area ◽  
Large Airway

The cause-and-effect relationship between airway smooth muscle (ASM) remodeling and airway hyperresponsiveness (AHR) following allergen challenge is not well established. Using a rat model of allergen-induced ASM remodeling we explored the relationship between the site of ASM remodeling and AHR. Brown Norway rats, sensitized and challenged (3 times at 5-day intervals) with ovalbumin, were intranasally administered 0.1 mg/kg budesonide 24 and 1 h before challenge. Airway responses to aerosolized methacholine were assessed 48 h or 1 wk after three challenges. Airways were stained and analyzed for total airway wall area, area of smooth muscle-specific α-actin, and goblet cell hyperplasia, and the constant-phase model was used to resolve the changes in respiratory system mechanics into large airway and peripheral lung responses. After three ovalbumin challenges, there was a significant increase in ASM area and in the total wall area in all sized airways as well as an increase in goblet cells in the central airways. Budesonide inhibited ASM growth and central airway goblet cell hyperplasia following ovalbumin challenges. Budesonide also inhibited small but not large airway total wall area. AHR was attributable to excessive responses of the small airways, whereas responsiveness of the large airways was unchanged. Budesonide did not inhibit AHR after repeated challenge. We conclude that ASM remodeling induced by repeated allergen challenges involves the entire bronchial tree, whereas AHR reflects alterations in the lung periphery. Prevention of ASM remodeling by corticosteroid does not abrogate AHR.

β-Catenin regulates differentiation of respiratory epithelial cells in vivo

2005 ◽  
Vol 289 (6) ◽  
pp. L971-L979 ◽  
Author(s):  
Michael L. Mucenski ◽  
Jennifer M. Nation ◽  
Angela R. Thitoff ◽  
Valérie Besnard ◽  
Yan Xu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Goblet Cell ◽  
Alveolar Type ◽  
Type Ii ◽  
Respiratory Epithelial Cells ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Air Space ◽  
Respiratory Epithelial ◽  
Conducting Airways

An activated form of β-catenin [CatnbΔ(ex3)] was expressed in respiratory epithelial cells of the developing lung. Although morphogenesis was not altered at birth, air space enlargement and epithelial cell dysplasia were observed in the early postnatal period and persisted into adulthood. The CatnbΔ(ex3) protein caused squamous, cuboidal, and goblet cell dysplasia in intrapulmonary conducting airways. Atypical epithelial cells that stained for surfactant pro protein C (pro-SP-C) and had morphological characteristics of alveolar type II cells were observed in bronchioles of the transgenic mice. CatnbΔ(ex3) inhibited expression of Foxa2 and caused goblet cell hyperplasia associated with increased staining for mucins and the MUC5A/C protein. In vitro, both wild type and activated β-catenin negatively regulated the expression of the Foxa2 promoter. CatnbΔ(ex3) also caused pulmonary tumors in adult mice. Activation of β-catenin caused ectopic differentiation of alveolar type II-like cells in conducting airways, goblet cell hyperplasia, and air space enlargement, demonstrating a critical role for the Wnt/β-catenin signal transduction pathway in the differentiation of the respiratory epithelium in the postnatal lung.

Nicotine does not cause ‘bronchitis’ in the rat

1986 ◽  
Vol 70 (5) ◽  
pp. 427-433 ◽  
Author(s):  
D. F. Rogers ◽  
Deborah A. Williams ◽  
P. K. Jeffery
Keyword(s):  
Secretory Cell ◽  
Plasma Concentrations ◽  
Cell Number ◽  
Major Constituent ◽  
Surface Epithelium ◽  
Secretory Cells ◽  
Nicotine Gum ◽  
Cell Hyperplasia ◽  
Specific Pathogen ◽  
Conducting Airways

1. Nicotine is of interest as a major constituent of cigarette smoke and as an additive to chewing gum used to help patients to stop smoking. 2. Specific pathogen-free rats were given an aerosol or injections of nicotine hydrogen (+) tartrate (l-isomer) for 2 or 3 weeks at three doses and the number of secretory cells in the surface epithelium of airways was determined. 3. By aerosol, a dose giving 10 ng of nicotine/ml of plasma had no effect on secretory cell number. 4. By injection, nicotine had a ‘bi-phasic’ effect depending on dose: it reduced secretory cell number at plasma concentrations of 650 ng/ml of plasma or increased it at 2360 ng/ml of plasma. 5. Thus nicotine alone, given to rats at doses similar to those found in cigarette smokers and those who chew nicotine gum, does not cause secretory cell hyperplasia in the conducting airways of the rat.

scholarly journals The Contribution of Small Airway Obstruction to the Pathogenesis of Chronic Obstructive Pulmonary Disease

2017 ◽  
Vol 97 (2) ◽  
pp. 529-552 ◽  
Author(s):  
James C. Hogg ◽  
Peter D. Paré ◽  
Tillie-Louise Hackett
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Molecular Mechanisms ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Major Site ◽  
Obstructive Pulmonary Disease ◽  
Airways Resistance ◽  
Conducting Airways ◽  
Normal Lungs

The hypothesis that the small conducting airways were the major site of obstruction to airflow in normal lungs was introduced by Rohrer in 1915 and prevailed until Weibel introduced a quantitative method of studying lung anatomy in 1963. Green repeated Rohrer's calculations using Weibels new data in 1965 and found that the smaller conducting airways offered very little resistance to airflow. This conflict was resolved by seminal experiments conducted by Macklem and Mead in 1967, which confirmed that a small proportion of the total lower airways resistance is attributable to small airways <2 mm in diameter. Shortly thereafter, Hogg, Macklem, and Thurlbeck used this technique to show that small airways become the major site of obstruction in lungs affected by emphysema. These and other observations led Mead to write a seminal editorial in 1970 that postulated the small airways are a silent zone within normal lungs where disease can accumulate over many years without being noticed. This review provides a progress report since the 1970s on methods for detecting chronic obstructive pulmonary disease, the structural nature of small airways' disease, and the cellular and molecular mechanisms that are thought to underlie its pathogenesis.

scholarly journals Pulmonary IL-1β expression in early life causes permanent changes in lung structure and function in adulthood

2018 ◽  
Vol 314 (6) ◽  
pp. L936-L945 ◽  
Author(s):  
Anna Hogmalm ◽  
Maija Bry ◽  
Kristina Bry
Keyword(s):  
Early Life ◽  
Pulmonary Inflammation ◽  
Structure And Function ◽  
Small Airways ◽  
Pulmonary Epithelium ◽  
Airway Reactivity ◽  
Cell Hyperplasia ◽  
Lung Structure ◽  
And Function ◽  
The Impact

Chorioamnionitis, mechanical ventilation, oxygen therapy, and postnatal infection promote inflammation in the newborn lung. The long-term consequences of pulmonary inflammation during infancy have not been well characterized. The aim of this study was to examine the impact of inflammation during the late saccular to alveolar stages of lung development on lung structure and function in adulthood. To induce IL-1β expression in the pulmonary epithelium of mice with a tetracycline-inducible human IL-1β transgene, doxycycline was administered via intraperitoneal injections to bitransgenic pups and their littermate controls on postnatal days (PN) 0, 0.5, and 1. Lung structure, inflammation, and airway reactivity were studied in adulthood. IL-1β production in early life resulted in increased numbers of macrophages and neutrophils on PN21, but inflammation subsided by PN42. Permanent changes in alveolar structure, i.e., larger alveoli and thicker alveolar walls, were present from PN21 to PN84. Lack of alveolar septation thus persisted after IL-1β production and inflammation had ceased. Early IL-1β production caused goblet cell hyperplasia, enhanced calcium-activated chloride channel 3 (CLCA3) protein expression, and increased airway reactivity in response to methacholine on PN42. Lymphoid follicles were present adjacent to small airways in the lungs of adult bitransgenic mice, and levels of the B cell chemoattractant CXC-motif ligand (CXCL) 13 were elevated in the lungs of bitransgenic mice compared with controls. In conclusion, IL-1β-induced pulmonary inflammation in early life causes a chronic lung disease in adulthood.

scholarly journals AB0511 INTERNATIONAL CONSENSUS ON ANCA TESTING AND INTERPRETATION BEYOND SYSTEMIC VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1553.2-1553
Author(s):  
S. Moiseev ◽  
J. W. Cohen Tervaert ◽  
Y. Arimura ◽  
D. Bogdanos ◽  
C. Elena ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
Lupus Erythematosus ◽  
Inflammatory Bowel Diseases ◽  
Systemic Vasculitis ◽  
Connective Tissue Diseases ◽  
Idiopathic Interstitial Pneumonia ◽  
Small Vessel Vasculitis ◽  
Research Support ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background:ANCA can be detected in sera from patients with autoimmune, inflammatory, infectious or neoplastic diseases.Objectives:To issue a Consensus Statement on ANCA testing and interpretation beyond systemic vasculitis.Methods:This Statement was prepared by a group of experts, based on the results of a comprehensive search in PubMed.Results:In certain settings beyond systemic vasculitis, ANCA may have diagnostic, clinical, and/or prognostic relevance. Testing for PR3- and MPO-ANCA by specific immunoassays should be performed in any patient with clinical features suggesting ANCA-associated vasculitis and in patients with anti-GBM disease and idiopathic interstitial pneumonia. Routine ANCA testing is not recommended in patients with connective tissue diseases (CTD), autoimmune liver diseases, inflammatory bowel diseases, infections, and/or malignancy unless there is evidence for small vessel vasculitis. ANCA testing by specific immunoassays may be useful in patients with rheumatoid arthritis, systemic sclerosis or primary Sjögren’s syndrome who have kidney disease with a nephritic sediment or in patients with systemic lupus erythematosus if a kidney biopsy shows prominent necrotizing and crescentic lesions or proliferative lupus nephritis. ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1, who do not have conventional disease-related autoantibodies, or in patients with inflammatory bowel diseases in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn’s disease. In these cases, ANCA should be tested by indirect immunofluorescence since target antigens are not well characterized. ANCA against bactericidal/permeability-increasing protein may be a biomarker for deteriorating lung function and a poor prognosis in patients with cystic fibrosis.Conclusion:ANCA testing is clinically relevant not only in patients with manifestations suggesting systemic vasculitis, but also in patients with certain other disorders, particularly in patients with anti-GBM disease or idiopathic interstitial pneumonia.Disclosure of Interests:Sergey Moiseev Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Jan Willem Cohen Tervaert: None declared, Yoshihiro Arimura: None declared, Dimitrios Bogdanos: None declared, Csernok Elena: None declared, Jan Damoiseaux: None declared, Marc Ferrante: None declared, Luis Felipe Flores-Suárez: None declared, Marvin Fritzler: None declared, Pietro Invernizzi: None declared, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim, J. Charles Jennette: None declared, Mark Little: None declared, Stephen P. McAdoo: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Charles D. Pusey: None declared, Antonella Radice: None declared, Alan D. Salama: None declared, Judith Savige: None declared, Mårten Segelmark: None declared, Yehuda Shoenfeld: None declared, Renato Alberto Sinico: None declared, Maria Jose Rego de Sousa: None declared, Ulrich Specks: None declared, Benjamin Terrier: None declared, Athanasios Tzioufas: None declared, Severine Vermeire: None declared, Ming-hui Zhao: None declared, Xavier Bossuyt: None declared

scholarly journals Long-acting muscarinic antagonists and small airways: which link?

2020 ◽  
Author(s):  
Mario Cazzola ◽  
Luigino Calzetta ◽  
Maria Gabriella Matera
Keyword(s):  
Potential Benefit ◽  
Experimental Studies ◽  
Internal Diameter ◽  
Small Airways ◽  
Local Inflammation ◽  
Inflammatory Stimuli ◽  
Vagal Innervation ◽  
Long Acting ◽  
Airway Tone ◽  
The Relationship

Involvement of small airways, those of less than 2 mm in internal diameter, is present in all stages of asthma and contributes substantially to the pathophysiologic expression of asthma. Therefore, small airways are increasingly viewed as a potential target in optimal asthma control. Airway tone, which is increased in asthma, is mainly controlled by the vagus nerve that releases acetylcholine (ACh) and activates muscarinic ACh receptors (mAChRs) post-synaptically on airway smooth muscle (ASM). In small airways, M3 mAChRs are expressed, but there is no vagal innervation. Non-neuronal ACh released from the epithelial cells that may express choline acetyltransferase (ChAT) in response to inflammatory stimuli, as well as from other structural cells in the airways, including fibroblasts and mast cells, can activate these receptors. By antagonizing M3 mAChR, the contraction of the ASM is prevented and, potentially, local inflammation can be reduced and the progression of remodeling may be affected. In fact, ACh also contributes to inflammation and remodeling of the airways and regulates the growth of ASM. Several experimental studies have demonstrated the potential benefit derived from the use of mAChR antagonists, mainly long-acting mAChR antagonists (LAMAs), on small airways in asthma. However, there are several confounding factors that may cause a wrong estimation of the relationship between LAMAs and small airways in asthma.

Small Airways Disease Caused by Mineral Dusts

1998 ◽  
Vol 13 (8) ◽  
pp. 617-620
Author(s):  
Andrew Churg ◽  
Joanne L. Wright
Keyword(s):  
Small Airways ◽  
Mineral Dusts
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