Restrictive lung disease Lecture four

Restrictive Lung Disease Mostly cause is unknown Equal decline in FEV1 & FVC

Diffuse Interstitial Disease Spectrum of diseases that involves pulmonary connective tissue . Many of the diseases have a similar clinical picture and an unknown etiology Present with dyspnea, tachypnea, crackles, cyanosis, and wheezing. Pulmonary function tests show decreased diffusing capacity, lung capacity, and compliance Chest x-ray shows irregular lines or a ground glass appearance Eventual pulmonary hypertension, cor pulmonale, and honeycomb lung occur. Pathogenesis: thought to be inflammatory Frequency: pneumoconiosis (25%), sarcoidosis (20%), idiopathic pulmonary fibrosis (15%), and collagen vascular disease (10%) Connective tissue= basement membrane, elastic tissue, collagen, mast cells, fibroblasts

Idiopathic Pulmonary Fibrosis Fibrosing disease of unknown cause Diagnosis is based on constellation of factors: clinical presentation, radiology, and pathology Thought to be caused by repeated bouts of alveolitis with fibroblastic healing The pathologic correlate is usual interstitial pneumonia (UIP) Clinical course :- Patients usually present between 40 and 70 years of age with a dry, relentless cough. Progresses to dyspnea, cyanosis, and heart and lung failure Patients usually die within three years of diagnosis Lung transplant is the only effective treatment

Idiopathic Pulmonary Fibrosis/ Usual Interstitial Pneumonia

Cryptogenic Organizing Pneumonia Consists of loose connective tissue plugs in the acini and terminal bronchioles. No evidence of interstitial fibrosis Formerly known as bronchiolitis obliterans with organizing pneumonia Most patients have a spontaneous regression, and require months of steroid treatment Similar histologic and clinical patterns can occur in the presence of other insults. Other insults- pneumonia (bacterial and viral), drugs, collagen vascular disease, inhaled toxins, GVHD

Collagen Vascular Disease Many different collagen vascular diseases affect the lung architecture lupus, scleroderma, rheumatoid arthritis, and mixed connective tissue disease are some examples Lung involvement is highly variable between diseases and between individual cases of each disease Pattern of involvement is also highly variable has four different patterns of lung involvement ranging from chronic pleuritis to fibrosis to pulmonary hypertension.

Pneumoconiosis

Pneumoconiosis Non-neoplastic lung disease caused by a wide variety of particulates, vapors, and fumes. Originally documented as exposures in the workplace, but is now extending to exposures in the population from ambient air exposure Effects can vary widely from patient to patient and depend largely on the agent the person was exposed to and the degree of exposure

Pneumoconiosis Pathogenesis In general, development and extent of disease depends on four variables: Amount of agent in the lungs- depends on concentration of exposure, duration of exposure and clearance mechanisms Size and shape , Solubility and toxicity of particles- smaller particles rest in terminal airways and alveoli causing more damage Additional effects of other irritants- e.g. smoking and asbestos exposure

Coal Workers’ Pneumoconiosis (CWP) Results from exposure to coal dust Response to exposure varies greatly from person to person. Most are asymptomatic. The range of host responses varies from asymptomatic anthracosis to simple CWP to complicated CWP, or progressive massive fibrosis. Complicated CWP is the only one of clinical concern

Coal Induced Pulmonary Lesions Anthracosis- has no deleterious effect on patients. Manifests as black carbon streaks in lymphatics and nodes. Carbon is also ingested by macrophages. Present in majority of autopsies, because it is also seen in people that smoke or live in urban areas Simple CWP- characterized by coal macules and nodules. They are primarily located near bronchioles in the lower lung lobes. Rarely can lead to centilobular emphysema Complicated CWP (Progressive massive fibrosis)- is a progression from sCWP and takes years to develop. Consists of multiple confluent large black fibrotic scars (“black lung”). Terminal progression leads to pulmonary hypertension and corpulmonale, along with respiratory failure

Gross of “Black Lung”

Silicosis and Asbestosis Also forms of pneumoconiosis Silicosis- most prevalent occupational disease. Caused by inhalation of silica. Progression is similar to that of CWP. Silicosis also causes active secretion of inflammatory mediators by macrophages Carries an increased risk of tuberculosis Also causes PMF similar to other pneumoconiosis Exposure to large concentrations of silica can lead to acute disease Silicosis- two forms crystaline and amorphous. Crystaline (quartz and tridymite) more fibrogenic

Silicosis and Asbestosis Asbestos- crystalline fibers of silicates that form sheets. Used widely in insulation and heat resistant products Asbestos exposure is linked to fibrous plaques, pleural effusions, interstitial fibrosis, lung cancer, mesothelioma. Characteristic that sets asbestos apart is its ability to induce neoplasm formation. Also acts in synergy with other carcinogens about 5x risk of lung cancer in asbestos workers; about 55x risk of lung cancer in asbestos workers that smoke. Also, and about 1000x risk of mesothelioma in asbestos workers. Asbestos reaches deep into the lung parenchyma and can reach the parietal surface forming collagenous plaques

Treatment Induced Pulmonary Disease Drugs have been known to produce a wide range of pulmonary side effects from bronchospasm to ARDS to fibrosis. Bleomycin and amiodarone- fibrosis and pneumonitis Aspirin and beta blockers- bronchospasm Dozens of drugs- allergic hypersensitivity Radiation causes a wide range of pulmonary complications. Pneumonitis and subsequent fibrosis are well documented effects. Acutely the patient has fever and dyspnea Some patients do not resolve and progress to fibrosis

Sarcoidosis A systemic disease that has been known to affect almost any organ in the body Characterized by non-caseating granulomas Presents most often with bilateral hilar lymphadenopathy, fever, fatigue, and SOB Also presents with ocular and skin lesions Most prevalent in African American blacks, women, and people from the Southeast Etiology is unknown. Thought to be a T cell hyperresponse to an unknown antigen. Genetic factors are implicated- clustering in families and races.

Effects of Sarcoidosis Pulmonary- grossly normal, but microscopically there are diffuse granulomas. Fibrosis and amyloid deposition occur. Pulmonary hypertension and cor pulmonale ensue Systemic effects- eye- iritis, corneal opacities, glaucoma, vision loss Skin- very common, nodules or erythematous plaques Oral cavity- similar plaques and nodules of the skin Muscle- weakness, tenderness, fatigue Spleen, bone marrow- diffuse replacement with granulomas

Sarcoidosis

Hypersensitivity Pneumonitis Hypersensitivity pneumonitis- an immunologically mediated interstitial lung disorder caused by prolonged exposure to an offending environmental agent The agent is normally organic and related to occupations or hobbies: Bird fancier’s lung Farmer’s lung Patients present with fever, dyspnea, cough, often associated with exposure to antigen. Represents a hypersensitivity reaction involving alveoli, not bronchioles. Removal of the offending antigen is essential to prevent terminal fibrosis Pathogenesis of hypersensitivity pneumonitis involves immune complex formation and delayed hypersensitivity

Smoking Related Interstitial Disease Desquamative Interstitial Pneumonia (DIP)- collection of macrophages with brown pigment in the airspaces. Not squamous cells. Thickened septa lined by reactive pneumocytes. Presents in 40’s and 50’s with cough, dyspnea, clubbing All patients are smokers Steroid therapy and smoking cessation is curative Respiratory Bronchiolitis- similar collection of macrophages as seen in DIP, but macrophages are located in the bronchioles. “Respiratory bronchiolitis-associated interstitial lung disease”- given to those with significant symptoms, or radiologic abnormalities Mild dyspnea, cough in smokers around 40-60 Smoking cessation is curative

Vascular lung disease

Pulmonary Embolism Common. Causes almost 50,000 deaths/yr Blood clots that occlude the pulmonary artery Vast majority are from lower extremities Risk factors- Virchow’s triad- stasis, hypercoaguable states, injury Burn, trauma, cancer, and immobile patients Presenting symptoms Effects depend on size of occulsion Respiratory compromise is frequent Sudden death due to saddle embolus or critical compromise of respiratory function

Pulmonary Hypertension Normal pressure within the pulmonary artery vasculature is 13-17 mmHg. Elevation of this normal pressure to approximately 25 mmHg and over is pulmonary hypertension Can be primary or secondary. Most disease is secondary to abnormalities that increases pulmonary artery blood flow or pressure: Chronic obstructive or restrictive lung disease Congenital or acquired heart disease- e.g. mitral stenosis Recurrent thromboembolism Autoimmune disorders- e.g. scleroderma directly involves pulmonary vasculature causing sclerosis Primary is usually sporadic and no other cause can be identified. 6% of primary are autosomal dominant with incomplete penetrance of 10-20%

Pulmonary Hypertension Histologic morphology Medial hypertrophy, intimal fibrosis, stenosis Extreme cases-plexogenic pulmonary arteriopathy

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