Hypersensitivity – aka (extrinsic allergic alveolitis)
Hypersensitivity Pneumonitis is a disease that most commonly affects the midlung field Next in frequency are the upper lung field and lastly diffuse involvement. Anatomically the small airways and the alveoli are affected with inflammation and granulomas are present Ashley Davidoff MD TheCommonvein.net lungs-0732b01
A normal bronchiole usually 1mm or less in diameter. The wall consists of ciliated cuboidal epithelium and a layer of smooth muscle. Bronchioles divide into even smaller bronchioles, called terminal bronchioles, which are 0.5 mm or less in diameter and are primarily lined by club cells, and accompanied by a small number of ciliated cuboidal cells.. Respiratory bronchioles are the final division of the bronchioles within the lung and they are .5mm or less in diameter and contain a simple non ciliated cuboidal epithelium and a thin layer of smooth muscle Ashley Davidoff MD TheCommonVein.net lungs-0721
Smoking excites the Langerhans cell which in turn induces and attracts early cellular interstitial infiltrates which surround the bronchiole. The diagram shows a bronchiole surrounded by an acute cellular inflammatory response Ashley Davidoff MD TheCommonVein.net lungs-0722
=
Alveolitis
Cellular Bronchiolitis
Granulomas
acute, subacute, and chronic/fibrotic
Immune reaction – inflammation to an
allergen
protein
microbe
animal protein
plant protein
hapten = low molecular wt protein combining with host protein becomes immunogenic
Smoking
95% of pts with HP are non smokers
5% smokers with HP have a high mortality
Pneumonitis –
Terminal bronchiole and alveoli
Nutshell Buzz
Airway Thickening
Alveolitis
Acute stage
Diffuse Alveolar Damage
Increased permeability
Neutrophils
neutrophillic exudate
Exudate
Radiology
GGO’s
Consolidation
Position
bilateral
midlung >upper lung >diffuse
only lower lungs does not happen
Shape
Ill defined
Patchy and or
Nodular Infiltrates
Bird Fanciers Disease
Acute Hypersensitivity Pneumonitis
Upper and Mid Lung Field
Mild Ground Glass Changes Acute Hypersensitivity Pneumonitis 54-year-old female who keeps parakeets present with mild dyspnea Chest CT shows mild ground glass changes in the mid and upper lung fields consistent with acute hypersensitivity pneumonitis (HP) Ashley Davidoff TheCommonVein.net 136571
Mild Ground Glass Changes Acute Hypersensitivity Pneumonitis 54-year-old female who keeps parakeets present with mild dyspnea Chest CT shows mild ground glass changes in the mid and upper lung fields consistent with acute hypersensitivity pneumonitis (HP) Ashley Davidoff TheCommonVein.net 136573
Nodular
Aspiration Pneumonia Pulmonary Edema and DAD 54 year old male alcoholic with seizures presents with diffuse alveolar disease consistent with pulmonary edema (a). CT scan (b) shows bibasilar infiltrates consistent with aspiration. Follow up CXR 6 months later (c) shows resolution Ashley Davidoff MD TheCommonVein.net
Non Fibrotic = Subacute Phase
Structurally
Small Airways
Poorly Defined Ground Glass Nodules
Alveoli – Alveolitis =
Combined Small Airway and Alveol i
3 density sign = head cheese sign
Disease
Inflammation
Cellular Infiltrate and Edema
Around Bronchioles
Around Alveoli =
Alveolitis –
lungs-0021catalogue-signed-smallb.jpg
Inflamed Alveoli Ashley Davidoff MD TheCommonvein.net lungs-0021
Inflammation in the Wall of the Alveoli = Interstitial Infiltrate
High magnification photomicrograph of a lung biopsy taken showing chronic hypersensitivity pneumonitis (H&E), showing mild expansion of the alveolar septa (interstitium) by lymphocytes.[clarification needed] A multinucleated giant cell, seen within the interstitium to the right of the picture halfway down, is an important clue to the correct diagnosis. Courtesy Wikiwand web lungs 435
Granulomas around the bronchiole or arteriole
Impinging on the Lumen of a Centrilobular Bronchiole
Granuloma Impinges on the lumen of the centrilobular bronchiole The peri- bronchiole inflammation has receded in this subacute to chronic phase Ashley Davidoff MD TheCommonVein.net lungs-0729
Granulomas around the bronchiole or arteriole
Occluding the Lumen of a Centrilobular Bronchiole
Granuloma occludes the lumen of the centrilobular bronchiole and the peri-bronchiole inflammation has receded in this subacute to chronic phase Ashley Davidoff MD TheCommonVein.net lungs-0731
Diagnosis
Mid Lung Fields> Upper Lung Fields > Diffuse
Bronchiolitis
Alveolitis
Granulomas
GGO
reticlonodular
Reticulation
Ground Glass
Heterogeneous
Lobular sparing air trapping mosaic attenuation
Head Cheese Sign
Head cheese or brawn is a cold cut terrine or meat jelly, often made with flesh from the head of a calf or pig (less commonly a sheep or cow), typically set in aspic, that originated in Europe. Usually eaten cold, at room temperature, or in a sandwich, the dish is, despite the name, not a dairy cheese. The parts of the head used in the dish vary, though commonly do not include the brain, eyes or ears of the animal. The tongue, and sometimes the feet and heart of the animal may be included; the dish is also made using trimmings from more commonly eaten cuts of pork and veal, with the addition of gelatin as a binding agent. Head cheese may also be made without using the flesh from the head of an animal. Courtesy Rainer Zenz source Wiki
Structural focus
A normal bronchiole usually 1mm or less in diameter. The wall consists of ciliated cuboidal epithelium and a layer of smooth muscle. Bronchioles divide into even smaller bronchioles, called terminal bronchioles, which are 0.5 mm or less in diameter and are primarily lined by club cells, and accompanied by a small number of ciliated cuboidal cells.. Respiratory bronchioles are the final division of the bronchioles within the lung and they are .5mm or less in diameter and contain a simple non ciliated cuboidal epithelium and a thin layer of smooth muscle Ashley Davidoff MD TheCommonVein.net lungs-0721
Normal Small Airways
The Acinus, The Duct, and the Artery The pulmonary arteriole accompanies the airway as it carries oxygen from the trachea to the alveoli. They part ways at the alveoli where the pulmonary venule then takes the oxygenated blood from capillary network around the alveoli back to the left atrium. The intimate relationship of the airways and the pulmonary artery and their close approximation in size, is helpful in radiology, firstly to identify theese structures and secondly to define disease such as heart failure and bronchiectasis. The acinus as shown in this image is defined as a unit of lung consisting of a single first order respiratory bronchiole that subtending a cluster of alveoli reminiscent of a bunch of grapes or berries (acinus in Latin means berry) . The lobular bronchiole (lb) branches into the terminal bronchiole (tb), which then branches into the first order respiratory bronchiole (rb). Subsequent branching after the respiratory bronchiole, includes in order, the alveolar duct (ad), alveolar sac (as), and then finally the berry like alveoli. Courtesy Ashley Davidoff 2019 lungs-0033-low res
Respiratory Bronchioles This slide shows the transition from a terminal bronchiole, with a low cuboidal epithelium, to respiratory bronchioles, with a squamous epithelium. Terminal bronchioles are last generation of conducting airways. Respiratory bronchioles can be identified by the presence of some alveoli along their walls. The respiratory bronchiole splits into a number of alveolar ducts, which terminate in alveolar sacs and individual alveoli Courtesy medcell.med.Yale.edu
Non-specific severe chronic inflammation of a terminal bronchiole. Courtesy Dr Yale Rosen
The Alveolus – The Buck Ends Here The alveolus is lined by a simple epithelium ? one cell layer thick. There are two types of lining cells; Type 1 pneumocytes are squamous cells that cover 90% of the surface of the inner lining of the lung , and type II cuboidal pneumocytes that are in fact much more numerous than Type I. They are involved in the production of surfactant . In the lumen there are resident macrophages which play a crucial role in the immune system. The mucosa is grounded by a basement membrane and a lamina propria, and connected to the lamina propria and basement membrane of the surrounding capillary. The alveolus is lined by a thin layer of surfactant. (teal blue) Ashley Davidoff TheCommonVein.net
Magnification of Normal Histology of the Lung Lower magnification of the lung with H and E stain shows cup-shaped alveolar spaces outlined by delicate thin alveolar capillary membrane. key words lung, pulmonary, normal alveolus, alveoli, histology, interstitium, interstitial Courtesy Armando Fraire MD. 32819
High magnification photomicrograph of a lung biopsy taken showing chronic hypersensitivity pneumonitis (H&E), showing mild expansion of the alveolar septa (interstitium) by lymphocytes.[clarification needed] A multinucleated giant cell, seen within the interstitium to the right of the picture halfway down, is an important clue to the correct diagnosis. Courtesy Wikiwand web lungs 435 Acute
Abrupt onset
Flu like symptoms
malaise
Note
patients with fibrotic HP often overlap with those described in patients with idiopathic interstitial pneumonias – UIP and NSIP
distinction between
IPF and an inflammation-driven disorder such as fibrotic HP
is crucial, because
immunosuppressive therapy is considered to be harmful in IPF
appropriate in fibrotic HP.
On the other hand
anti-fibrotic treatment licensed for IPF,
not for fibrotic HP.
/www.youtube.com/watch?v=CPwRi6DO5VY
Hypersensitivity Pneumonitis High-resolution CT: increase in density in areas of ground glass and air trapping in lower lobes in a patient with hypersensitivity pneumonitis Courtesy Mluisamtz11
41-year-old man with subacute hypersensitivity pneumonitis. High-resolution CT image shows bilateral poorly defined centrilobular nodules and ground-glass opacities. Also evident are lobular areas (arrows) of decreased attenuation.
41-year-old man with subacute hypersensitivity pneumonitis. Expiratory high-resolution CT scan at same level as A shows air trapping in lobules (curved arrows) that had decreased attenuation on inspiratory CT and in other lung regions (straight arrow).
Hypersensitivity pneumonitis. (a) Axial and (b) coronal images from CT scan in lung windows in a 28-year-old woman who presented with chronic cough associated with shortness of breath dyspnea on exertion. She lives at home, where her sister has an African gray parrot. Images show widespread ground-glass opacities. There is hypoattenuation and hypovascularity of scattered secondary lobules (head cheese sign). Her clinical symptoms worsened, and she was diagnosed with hypersensitivity pneumonitis.Parekh, M et al Review of the Chest CT Differential Diagnosis of Ground-Glass Opacities in the COVID Era Radiology Vol. 297, No. 3 July 2020
Hypersensitivity Pneumonitis
Hypersensitivity pneumonitis
Hypersensitivity pneumonitis GGO Non fibrotic
Hypersensitivity pneumonitis Air trapping
Fibrotic HP
Upper lobe predominance
Fibrotic Hypersensitivity pneumonitis
Small Airway Disease Terminal Bronchiole
Small Airway Disease Giant Cell Around the Terminal Bronchiole
Hypersensitivity pneumonitis Multinucleate giant cells within a terminal bronchiole. Courtesy Dr Yale Rosen
Small Airway Disease – Organizing Pneumonia – Terminal Bronchiole
Hypersensitivity pneumonitis-organizing pneumonia Case 129 Areas of organizing pneumonia are frequently seen in hypersensitivity pneumonitis. Courtesy Dr Yale Rosen
Interstitial Infiltrates
Hypersensitivity pneumonitis Mild interstital inflammation and multiple granulomas. Courtesy Dr Yale Rosen
Hypersensitivity pneumonitis Interstitial chronic inflammation and a granuloma composed of multinucleate giant cells. Courtesy Dr Yale Rosen
Hypersensitivity pneumonitis Mild interstital inflammation and multiple granulomas. Courtesy Dr Yale Rosen
Hypersensitivity pneumonitis An interstitial granuloma composed of multinucleate giant cells. Courtesy Dr Yale Rosen
Hypersensitivity pneumonitis Patchy chronic interstitial inflammation and a granuloma composed of multinucleate giant cells. Courtesy Dr Yale Rosen
High magnification photomicrograph of a lung biopsy taken showing chronic hypersensitivity pneumonitis (H&E), showing mild expansion of the alveolar septa (interstitium) by lymphocytes.[clarification needed] A multinucleated giant cell, seen within the interstitium to the right of the picture halfway down, is an important clue to the correct diagnosis. Courtesy Wikiwand web lungs 435
Nutshell Buzz
Low magnification view of the histology of chronic hypersensitivity pneumonitis. The interstitium is expanded by a chronic inflammatory infiltrate. Two multinucleated giant cells can be seen within the interstitium at left, and a plug of organizing pneumonia at bottom left. Courtesy Mutleysmith Wikipedia
High magnification micrograph of hypersensitivity pneumonitis showing granulomatous inflammation. Trichrome stain. Courtesy Nephron
7 Years Prior
CT Hypersensitivity Pneumonitis
Mild Thickening of the Interlobular Septa and prominence of Some Centrilobular Nodules
7 Years Prior CT Hypersensitivity Pneumonitis CT in the axial plain (upper panels) and coronal plane (lower panels) show most prominent changes in the anterior segment of the upper lobes The findings are characterized by evidence of thickening of the interlobular septa, nodular bronchovascular bundle and centrilobular nodules. indicating small airway disease Ashley Davidoff MD TheCommonVein.net 135836
6 Years Prior
Mild Progression of Thickening of the Interlobular Septa and Prominence of Some Centrilobular Nodules
6 Years Prior CT Hypersensitivity Pneumonitis CT in the axial plain (upper panels) and coronal plane (lower panels) show most prominent persistent changes in the anterior segment of the upper lobes The findings are characterized by evidence of thickening of the interlobular septa, nodular bronchovascular bundle and centrilobular nodules. indicating small airway disease Ashley Davidoff MD TheCommonVein.net 135837
5 Years Prior
Minimal Change
5 Years Prior CT Hypersensitivity Pneumonitis CT in the axial (upper)and coronal plane (lower panels) show most prominent progressive changes in the anterior segment of the left upper lobe The findings are characterized by evidence of thickening of the bronchovascular bundle and centrilobular nodules upper right panel) indicating small airway disease Ashley Davidoff MD TheCommonVein.net 135838
Current
Progressive Nodular Thickening Along the Bronchovascular Bundle and Enlarging Centrilobular Nodules
CT Hypersensitivity Pneumonitis Current CT in the axial (upper)and coronal plane (lower panels) show most prominent and progressive changes in the anterior segment of the left upper lobe The findings are characterized and by evidence of thickening of the bronchovascular bundle (upper right panel) and centrilobular nodules (lower right panel) indicating small airway disease Ashley Davidoff MD TheCommonVein.net 135839
CT Hypersensitivity Pneumonitis 7 years prior CT in the axial (upper)and coronal plane (lower panels) show most prominent changes in the anterior segment of the left upper lobe The findings are characterized and best appreciated in the upper right panel by evidence of small airway disease including tree in bud and centrilobular nodules most prominent in the periphery Ashley Davidoff MD TheCommonVein.net 135835
Hypersensitivity Pneumonitis Pattern
Hypersensitivity Pneumonitis Pattern
a- PD-1 inhibitor pneumonitis: Hypersensitivity pneumonitis pattern in a 68-year-old man with metastatic renal cell carcinoma who was treated with nivolumab and presented with a new cough at 6 months of therapy. (a) Axial chest CT image shows new multifocal GGOs in a centrilobular distribution throughout both lungs and mosaic attenuation, findings that represent pneumonitis with a hypersensitivity pneumonitis pattern. Nivolumab therapy was withheld, and the patient underwent corticosteroid therapy.
Nishino, M et al Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care RadioGraphicsVol. 37, No. 5
Hypersensitivity Pneumonitis Pattern
b
Axial follow-up CT image obtained after 1 month of corticosteroid therapy shows marked improvement of pneumonitis and resolution of GGOs. Nivolumab continued to be withheld, and corticosteroid therapy was tapered. At 1.5 months after completing the corticosteroid taper, without restarting nivolumab or any other systemic therapy, the patient experienced a worsening cough.
Nishino, M et al Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care RadioGraphicsVol. 37, No. 5
Hypersensitivity Pneumonitis Pattern
c
Axial chest CT image shows development of diffuse GGOs with areas of air trapping, findings indicative of pneumonitis with a hypersensitivity pneumonitis pattern. The radiographic pattern of this second episode is similar to that noted in the initial episode and represents pneumonitis flare.
Nishino, M et al Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care RadioGraphicsVol. 37, No. 5
Hypersensitivity Pneumonitis
Pneumonitis in a 62-year-old woman with advanced pancreatic neuroendocrine tumor treated with everolimus and temozolomide. Axial CT image obtained at 10.3 months of therapy shows diffuse bilateral GGOs and reticular opacities that are indicative of a hypersensitivity pneumonitis pattern. The patient had mild shortness of breath and was treated with prednisone.
Nishino, M et al Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care RadioGraphicsVol. 37, No. 5
Pneumonitis
Pneumonitis in a 42-year-old man with an EGFR exon 19 deletion mutation who was treated with erlotinib in the United States. Axial chest CT images (b obtained at a lower level than a) obtained at 8 weeks of therapy show multifocal areas of GGOs in both lungs, findings that represent pneumonitis. Note the absence of traction bronchiectasis or volume loss.
Nishino, M et al Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care RadioGraphicsVol. 37, No. 5
b) Pneumonitis
Pneumonitis in a 42-year-old man with an EGFR exon 19 deletion mutation who was treated with erlotinib in the United States. Axial chest CT images (b obtained at a lower level than a) obtained at 8 weeks of therapy show multifocal areas of GGOs in both lungs, findings that represent pneumonitis. Note the absence of traction bronchietasis or volume loss.
Nishino, M et al Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care RadioGraphicsVol. 37, No. 5
Nishino, M et al Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care RadioGraphicsVol. 37, No. 5
References and LINKS
ARRS Santiago Rossi
Wiki
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