Dr/ ABD ALLAH NAZEER. MD.

Radiological imaging of restrictive lung disease.

Restrictive lung diseases (Diffuse Interstitial Lung Disease) A heterogeneous group of disorders characterized predominantly by diffuse and usually chronic involvement of the pulmonary connective tissue. Fibrosis Stiff lung Which level? principally the most peripheral and delicate interstitium in the alveolar walls. This result in reduced expansion of lung with reduction in total lung capacity

Fibrosis.Stiff Lung.

Restrictive lung diseases (Interstitial lung disease) Important signs and symptoms: -Dyspnea. -Hypoxia (caused by damage to the alveolar epithelium and interstitial vasculature produces abnormalities in the ventilation- perfusion ratio) - With progressive severe hypoxia, respiratory failure and Cor pulmonale. - Chest radiographs show diffuse infiltration by small nodules, irregular lines, or "ground-glass shadows Restrictive lung diseases (Interstitial lung disease) Acute: edema in acute respiratory distress syndrome e.g. Adult respiratory distress syndrome Neonatal respiratory distress syndrome Acute edema in acute respiratory distress syndrome e.g. Adult respiratory distress syndrome, Neonatal respiratory distress syndrome. Chronic: chronic inflammation &fibrosis e.g. Pneumoconiosis Idiopathic pulmonary fibrosis. Sarcoidosis. Hypersensitivity pneumonitis Immune mediated: SLE Chemical related: berylliosis .

Acute Lung Injury (Adult respiratory distress syndrome (ARDS) Progressive respiratory insufficiency caused by diffuse alveolar damage in the setting of sepsis, severe trauma, and diffuse pulmonary infections.

Causes of ARDS: ARDS can be a manifestation of sever acute respiratory syndrome (SARS) SARS is a corona virus that destroys the type II pneumocytes and causes diffuse alveolar damage ACUTE LUNG INJURY Adult respiratory distress syndrome (ARDS) Diffuse alveolar damage with result in increase in alveolar capillary permeability leakage of protein-rich fluid into alveoli formation of an intra-alveolar hyaline membrane composed of fibrin and cellular debri ACUTE LUNG INJURY (ARDS_ The pulmonary infiltrates in acute lung injury are usually caused by damage to the alveolar capillary membrane by neutrophils or by ROS Result in non cardiogenic pulmonary edema.

ACUTE LUNG INJURY(ARDS) Clinical Manifestations 1. acute onset of dyspnea 2. decreased arterial oxygen pressure (hypoxemia) 3. development of bilateral pulmonary infiltrates on radiographs absence of clinical evidence of primary left-sided heart failure Manifestations appear within 72 hours of the initiating insult Clinical Course Historically, mortality rates approached 100%. Despite improvements in supportive therapy the mortality is still about 60%. Predictors of poor prognosis in ARDS include : advanced age, underlying bacteremia (sepsis) the development of multisystem (especially cardiac, renal, or hepatic) failure. RESPIRATORY DISTRESS SYNDROME OF THE NEWBORN hyaline membrane disease Pathogenesis RDS –is a disease of premature infants. –It occurs in about 60% of infants born at less than 28 weeks of gestation – Other causes: maternal diabetes cesarean section before the onset of labor twin gestation.

Anteroposterior (AP) portable chest radiograph in a patient who had been in respiratory failure for 1 week with the diagnosis of acute respiratory distress syndrome. This image shows an endotracheal tube, a left subclavian central venous catheter in the superior vena cava, and bilateral patchy opacities in mostly the middle and lower lung zones.

Portable chest radiograph in a patient with acute respiratory distress syndrome. The condition evolved over approximately 1 week.

A: Chest radiograph of patient with ARDS shows bilateral infiltrates. There is bilateral consolidation and a right pleural effusion. B: Chest radiograph of the same patient shows persistent bilateral infiltrates after 7 days.

Portable chest radiograph. This image shows bilateral opacities that are suggestive of ARDS.

Computed tomography scan in a patient with suspected acute respiratory distress syndrome (ARDS). This image was obtained at the cardiac level with mediastinal window settings and shows bilateral pleural effusions instead of diffuse bilateral lung consolidation. In addition, the presence of some compression atelectasis in the lower lobes is observed.

High-resolution computed tomography scan in a patient with acute respiratory distress syndrome. This image demonstrates a small right pleural effusion, consolidation with air-bronchograms, and some ground-glass-appearing opacities. The findings indicate an alveolar process, in this case, alveolar damage.

Computed tomogram of a patient with ARDS shows bilateral dense dependent consolidation, with areas of ground-glass opacification and normal lung in the non-dependent lung.

Computed tomogram in ARDS shows bilateral reticulation and ground-glass opacification, containing areas of bronchial dilatation in the upper lobes. In the acute phase of ARDS, bronchial dilatation may indicate fibrosis or may be reversible. Note also the pneumomediastinum identified by computed tomogram.

Computed tomogram of the mid zones of a patient with ARDS shows bilateral ground-glass opacification. Note the presence of non-dependent consolidation in the right lower lobe, which raises the possibility of superadded infection. The esophageal stent is incidental.

A: Computed tomogram shows bilateral dependent consolidation in a patient with ARDS, as well as ground-glass opacities in the non-dependent lung. B: Follow-up computed tomogram after 1 year shows resolution of the consolidation and ground-glass opacification with cyst formation in the anterior left lung.

CT images with post-traumatic ARDS.

CT images with post-traumatic ARDS.

X-ray after severe blunt trauma with ARDS.

Severe respiratory distress syndrome (RDS). Reticulogranular opacities are present throughout both lungs, with prominent air bronchograms and total obscuration of the cardiac silhouette. Cystic areas in the right lung may represent dilated alveoli or early pulmonary interstitial emphysema (PIE).

Chronic restrictive lung disease Major Categories of Chronic Interstitial Lung Disease (CILD) -Fibrosing: Pneumoconiosis, Usual interstitial pneumonia (idiopathic pulmonary fibrosis) Cryptogenic organizing pneumonia Associated with collagen vascular diseases Drug and Radiation Reactions -Granulomatous: Sarcoidosis Hypersensitivity pneumonitis. Wegener’s granulomatosis -Eosinophilic granuloma -Smoking related: Desquamative interstitial pneumonia Respiratory bronchiolitis-associated interstitial lung disease.Chronic Interstitial Lung disease CILD Many entities are of unknown cause and pathogenesis Similar clinical signs, symptoms, radiographic alterations and pathophysiologic changes. –Patient have reduced forced vital capacity, however the FEV1/ FVC is normal Account for about 15% of non-infectious lung diseases.

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) (Usual interstitial pneumonia) UIP A clinicopathologic syndrome with characteristic radiologic, pathologic and clinical features. –Radiology: Bilateral lung nodular infiltrate –Histology: diffuse interstitial fibrosis and inflammation. –Clinical features: Dyspnea, advanced cases result in sever hypoxemia and cyanosis. Males are more affected than female 2/3 of pt. older than 60 years Pathogenesis Some form of alveolar wall injury result in interstitial edema and alveolitis. Type I pneumocyte is more susceptible to injury. Type II pneumocyte hyperplasia (regenerate). Fibroblast proliferation with progressive fibrosis of intra-alveolar exudate and interalveolar septa. IgG deposits are seen in alveolar wall. IL-8 leukotriens FGF, TGF-, PDGF

Morphology of IPF Gross - The lungs are firm. -Pulmonary edema. The morphologic changes vary according to the stage of the disease. Early cases: -Intra-alveolar exudate. -Hyaline membranes. -Infiltration of the alveolar septa with mononuclear cells. -Hyperplasia of type II pneumocytes – Morphology of IPF Advancing disease: - Organization of the intra-alveolar exudates by fibrous tissue. -Thickening of the alveolar septa owing to fibrosis and variable amounts of inflammation. -Alternating areas of fibrosis and normal tissue. - Geographic variation - Temporal variation In the end, the lung consists of spaces lined by cuboidal or columnar epithelium separated by inflammatory fibrous tissue (honeycomb lung). Prognosis of IPF Gradual onset of dyspnea with respiratory difficulty. Hypoxemia and cyanosis. Cor pulmonale and cardiac failure may result. The progression in individual cases is unpredictable. The median survival is about 2 to 4 years.

Hypersensitivity pneumonitis An immunologically mediated inflammatory lung disease that primarily affects the alveoli and is therefore often called allergic alveolitis. Hypersensitivity to inhaled antigens in the form of organic substance: moldy hay, e.g. farmer’s lung, humidified lung or pigeon breeder’s lung. Hypersensitivity pneumonitis May present either as an acute reaction with fever, cough, dypsnea and constitutional complains 4 to 8 hours after exposure or as a chronic disease with insidious onset of cough, dyspnea, malaise and weight loss. Hypersensitivity pneumonitis Acute form result from the combination of: -A direct irritant effect. -Activation of the complement pathway -Immune complex Acute form result from the combination of: -A direct irritant effect. -Activation of the complement pathway -Immune complex Chronic form of the disease is mediated by delayed hypersensitivity reactions. Chronic form of the disease is mediated by delayed hypersensitivity reactions.

Pneumoconiosis Pathogenesis The development of pneumoconiosis is dependent on: -The amount of dust retained in the lung and airways. a. Concentration of the dust in the ambient air. b. Duration of the exposure. c. Effectiveness of the clearance mechanisms. -The size (1-5) shape. -Their solubility and physiochemical activity. -The possible additional effects of other irritants, tobacco smoking. The particles are impacted at alveolar duct macrophage, accumulate inflammatory response fibrosis.

Coal worker’s pneumoconiosis (CWP) Occurs in coal workers after many years of underground mine work. Two forms: -The simple form: - Focal aggregations of coal dust-laden macrophages (coal macules, 1 to 2 mm) mainly in upper lobes. - Patients have slight cough and blackish sputum. - emphysema ( smoking related).-The complicated form: With heavier pulmonary burdens of coal dust, fibrous scarring appears (complicated CWP) also called progressive massive fibrosis (PMF). Complicated CWP: - Black scars exceed 2 cm in diameter some times up to 10 cm -It consists of dense collagen and carbon pigments. -Cor pulmonale. -Miners who have rheumatoid arthritis and PMF are called Kaplan's syndrome. Coal worker pneumoconiosis Morphology: Clinical course: –CWP is usually benign disease with little symptom –Minor cases progress to PMF –No increased risk to bronchogenic carcinoma Coal worker pneumoconiosis

Silicosis Long exposure to silica particles. Nodular densely fibrosing pneumoconiosis. Encountered in a diversity of industries: mining of gold, tin, copper and coal, sandblasting, metal grinding, ceramic manufacturing, drilling and tunneling. Pathogenesis: Crystalline silica is highly fibrogenic. Scattered lymphocytes and macrophages are drawn rapidly with fibrosis. Some particles are transported to lymph nodes. Morphology of Silicosis Tiny collagenous nodules that enlarge forming stony-hard large fibrous scars usually in the upper lobes. The lung parenchyma between the scars may be compressed or emphysematous. Calcifications may appear (eggshell calcification). Similar collagenous nodules within the lymph nodes. Fibrous pleural plaques may develop. Forms of Silicosis Acute silicosis: –results from exposure to high dose of silica. Fluid in alveoli. – Pt. Have rapid onset of tachypnea, cough and respiratory failure. Chronic silicosis: –Inhalation of silica for long time with fibrotic nodules ( present in upper lobe of lung & in subpleural spaces Complicated silicosis: –Progression of chronic silicosis with PMF with chronic hypoxia Other pulmonary disease: –Increased susceptibility to TB –Caplan syndrome ( uncommon) –Lung cancer Silica and lung cancer The relationship between silica and lung cancer has been a contentious issue, but in 1997, based on evidence from several epidemiologic studies, the International Agency for Research on Cancer concluded that crystalline silica from occupational sources is carcinogenic in humans. However, this subject continues to be controversial.

Asbestosis Inhalation of asbestos leads to: -Asbestos pneumoconiosis. -Pleural effusion. -Pleural adhesions. -Parietal pleural fibrocalcific plaques. -Increased incidence of mesothelioma, bronchogenic carcinoma, laryngeal cancer. These consequences occurs decades after exposure has ended. An increased incidence of asbestos-related cancers in family members of asbestos workers has alerted the general public to the potential hazards of asbestos. Pleural plaque in asbestos Parietal pleura over dome of diaphragm.Asbestosis In asbestosis, pt. develop progressively worsened dyspnea with cough and sputum progressing to Cor pulmonale and death. Both bronchogenic carcinoma and mesothelioma develop in workers exposed to asbestos. The risk of bronchogenic carcinoma is fivefold and for mesothelioma is 1000 fold greater. The risk of bronchogenic carcinoma in 50 X increased in smoking asbestos workers (but not that of mesothelioma)

HRCT of advanced stage of idiopathic pulmonary fibrosis demonstrating reticular opacities with honeycombing, with predominant subpleural

distribution.

Idiopathic pulmonary fibrosis with bilateral lower lobe opacities and possible mild decrease in lung volumes

High-resolution CT (HRCT) shows increased pulmonary attenuation with distortion of the pulmonary architecture.

High-resolution CT (HRCT) shows distortion of the pulmonary architecture with thickening of pulmonary interstitium and some areas of ground-glass attenuation. No obvious honeycombing is present.

Imaging of idiopathic lung fibrosis in acute respiratory distress syndrome.

Cryptogenic organizing pneumonia

Cryptogenic organizing pneumonia

Cryptogenic organizing pneumonia.

Sarcoidosis with lung fibrosis.

Alveolar Sarcoid. Frontal chest radiograph at left demonstrates multiple, scattered mass-like densities with irregular margins. The disease affects primarily the periphery of the lungs. A CT scan of another patient with alveolar Sarcoid (right) shows multiple patchy densities with air bronchograms (black arrows).

Sarcoidosis with fibrosis in the upper lobes. X-Ray and Typical HRCT findings.

Acute hypersensitivity pneumonitis.

Acute hypersensitivity pneumonitis.

Subacute hypersensitivity pneumonitis with mosaic pattern.

Subacute hypersensitivity pneumonitis with ill-defined centrilobular nodules

Chronic hypersensitivity pneumonitis: Nonspecific chest film, typical HRCT-findings.

Chronic hypersensitivity pneumonitis.

Wegener granulomatosis shows heterogeneous airspace opacity, which occurs predominately in the lower lobes, and a focal ill-defined opacity in the right upper lobe. Findings are suggestive of pulmonary hemorrhage.

Wegener's granulomatosis on chronic immunosuppressant's and Aspergillus fumigatus super infection. Coronal high-resolution CT image shows large Wegener's granulomatosis cavity (arrow) super infected and Aspergillus fumigatus. Other cavities in left lung are related to Wegener's granulomatosis alone.

Transverse and coronal high-resolution CT images show ground-glass opacity with interlobular septal thickening and patchy consolidation throughout both lungs.

Renal biopsy confirmed diagnosis of Wegener's granulomatosis.

Acute bronchiolitis with generalized prominence of brochovascular markings in a perihilar distribution but no confluence consolidation or collapse.

Acute Bronchiolitis

Cellular bronchiolitis secondary to subacute hypersensitivity pneumonitis. High-resolution CT images through right mid lung show diffuse ill-defined centrilobular nodules with patchy

areas of low attenuation (arrows, A), probably representing air trapping.

Coal worker's lungs - chest x-ray.

Coal worker pneumoconiosis in a 62-year-old man who worked for 20 years in a coal mine. (a) Axial thin-section CT scan (1.0-mm-thick section) obtained at the level of the aortic arch shows numerous small centrilobular (arrows) and subpleural (arrowheads) nodules in both lungs

High-resolution CT images of advanced coal-worker's pneumoconiosis with parenchymal nodules, calcifications, and progressive and massive fibrosis.

Acute silicosis in a 52-year-old man who worked for 10 years as a crystal craftsman. (a, b) Axial thin-section CT scans (1.0-mm-thick sections) obtained at the levels of the ventricles (a) and the left basal truncal bronchus (b) show ground-glass opacities and mild interlobular septal thickening (arrows) in the middle and lower lobes of the right lung and in the lingular division of the upper lobe of the left lung, respectively.

Silicosis in a 56-year-old man who worked for 25 years as a stonecutter. (a) Chest radiograph shows multiple variable-sized nodular lesions in both lungs, predominantly in the upper and middle zones. (b) Axial thin-section CT scan (1.0-mm-thick section) obtained at the level of the azygos arch shows multiple small nodules with a perilymphatic (centrilobular plus subpleural) distribution in the upper lobe of both lungs. Note the tendency toward coalescence of the nodules in the lung periphery (arrows).

Silicosis and progressive massive fibrosis in a 58-year-old man who worked for 30 years as a stoneworker. (a) Chest radiograph shows multiple small nodules and masses in both lungs, predominantly in the upper and middle zones, and eggshell calcifications (arrows) in the lung hilum and the mediastinum. (b) Axial thin-section CT scan (1.0-mm-thick section) obtained at the level of the aortic arch shows large symmetric bilateral opacities with irregular margins (arrows) indicative of progressive massive fibrosis, as well as numerous small nodules and septal thickening (arrowheads).

Asbestos-Related Pleural Disease

Asbestosis in a 70-year-old man who worked for 30 years in a shipyard. (a, b) Axial thin-section CT scans (1.0-mm-thick sections) at the level of the suprahepatic inferior vena cava. (a) Scan obtained with lung window settings shows subpleural consolidation (arrow) in the lower lobe of the left lung, with reticulation, ground-glass opacities, and honeycombing. (b) Scan obtained with mediastinal window settings shows subpleural consolidation (arrow), pleural thickening (arrowheads) and effusion.

Asbestosis in a 59-year-old man who worked for 30 years at an automobile factory. (a) Axial thin-section CT scan (1.5-mm-thick section) obtained at the level of the liver dome with the patient prone shows small subpleural nodules (straight arrows), patchy ground-glass opacities (curved arrows), and interlobular septal thickening (arrowhead) suggestive of early-stage asbestosis. (b) CT scan obtained with mediastinal window settings at the level of the suprahepatic inferior vena cava shows band like pleural thickening (arrowheads) in the lower lobe of both lungs, a finding indicative of pleural plaque.

Malignant Mesothelioma Rare cancer of mesothelial cells Arise from parietal or visceral pleura Can arise from peritoneum and pericardium 50% of pt. have history of exposure to asbestos at work It also appeared in relatives of asbestos worker or in people living near asbestos factory The latent period between exposure and malignant mesothelioma is long (25 to 40 years) Nearly all cases are related to amphibole asbestos These minerals cannot be removed from the lung and the risk for malignant mesothelioma is life long Simian virus 40 (SV40) T antigen is found in 60 to 80% of malignant mesothelioma Characteristic E/M finding : numerous long microvilli on cell surface.

Malignant mesothelioma

Mesothelioma.

CT and Pet CT of mesothelioma.

Berylliosis in a 49-year-old man who worked for 7 years in metal polishing. (a) Chest radiograph shows bilateral mediastinal and hilar lymph node enlargement, as well as internal fixation of a right clavicular fracture. (b, c) Axial thin-section CT scans (1.0-mm-thick-sections) obtained at the levels of the bronchus intermedius (b) and the basal segmental bronchus (c) show multiple small nodules along the brochovascular bundles (straight arrows) and in sub fissural regions (arrowheads) and enlarged hilar lymph nodes (curved arrows).

Talcosis in a 52-year-old man who worked for 8 years in magnesium silicate processing. Axial thin-section CT scan (1.5-mm-thick section) obtained at the level of the main bronchi shows dense consolidation, with dilated bronchi, paracicatricial emphysematous changes (arrows), ground-glass opacities, and interlobular septal thickening (arrowheads) in the upper lobe of both lungs.

Siderosis in a 49-year-old man who worked for 8 years in a shipyard. Thin-section CT scan (1.5-mm-thick section) obtained at the level of the aortic arch shows multiple small and poorly defined centrilobular nodules (arrows) in the upper lobe of both lungs.

Eosinophilic granulomaLangerhans Cell Histiocytosis.

SUMMARY: ARDS is a clinical syndrome of progressive respiratory insufficiency caused by diffuse alveolar damage. The setting are : sepsis, severe trauma, and diffuse pulmonary infections. There is an imbalance of pro- and anti-inflammatory mediators causing acute inflammatory injury to the alveolar epithelium and capillary endothelium. Neutrophils and their products have a crucial role in the pathogenesis of ARDS. The characteristic histologic picture is that of alveolar edema, epithelial necrosis, accumulation of neutrophils, and presence of hyaline membranes lining the alveolar ducts.

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