Obstructive/Restrictive Lung Diseases Flashcards
mild, moderate, vs. severe asthma pathology?
Mild Asthma: edema and hyperemia of the mucosa and infiltration of the mucosa with mast cells, eosinophils, and lymphocytes.
Moderate Asthma: chemokines eotaxin, RANTES, macrophage inflammatory protein 1 alpha, and interleukin 8 lead to inflammation and smooth muscle constriction
Severe: hypertrophy and hyperplasia of airway glands and smooth muscle lead to severe airway thickening
asthma categories?
Mild intermittent: symptoms present for 2 days/week or less, or 2 nights/month or less (give shorta acting albuterol)
Mild persistent: symptoms present for > 2 days/week but less than once daily, or > 2 nights/ month (SABA, ihnaled corticosteroid)
Moderate persistent: symptoms present daily or greater than once/night (SABA as needed, low/med dose of corticosteroid, LABA)
Severe persistent asthma: symptoms are continual during the day and frequent at night (SABA as needed, high dose corticosteroid, LABA)
Omalizumab
another tx for asthma - monoclonal antibody in patients with moderate to severe persistent asthma who have shown reactivity to an allergen and whose symptoms are inadequately controlled by an inhaled corticosteroid.
bronchiectasis in upper lobe?
think CF
bronchiectasis in lower lobe?
think aspiration
bronchiectasis in right middle lobe with lingular predominance
MAI
bronchiectasis in center of lung
bronchopulmonary aspergillosis
acute farmer’s lung?
Develops after large exposure to moldy hay or contaminated compost
Symptoms often spontaneously resolve within 12 hours to days if antigen exposure is eliminated or avoided
Acute farmer’s lung manifest as new onset of fever, chills, nonproductive cough, chest tightness, dyspnea, headache , and malaise.
If the inhalational exposure is large, patients may develop acute respiratory failure
subacute farmer’s lung?
Manifest as chronic cough, dyspnea, anorexia, and weight loss
Subacute disease is insidious in onset and may occur over weeks to months.
Chronic Farmer’s Lung
Results from prolonged and continuous exposure to antigen
Patients may have irreversible lung damage
Patients may experience severe dyspnea at rest or with exertion
Samter’s triad
ASA, NSAID sensitivity –> nasal polyps and asthma
allergic bronchopulmonary aspergillosis?
tx: prednisone
Occurs in asthmatics and CF patients from a hypersensitivity reaction to Aspergillus colonization of the tracheobronchial tree
This syndrome may cause fever and pulmonary infiltrates that are unresponsive to antibacterial therapy.
Patients often have a cough and produce mucous plugs, which may form bronchial casts. Possible hemoptysis.
People with asthma who have ABPA are usually poorly controlled asthmatics with difficulty tapering off oral corticosteroids
ABPA may occur in conjunction with allergic fungal sinusitis, with symptoms including chronic sinusitis with purulent sinus drainage.
sarcoidosis
Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized pathologically by the non-caseasting granuloma.
Can effect almost any organ
90% of patients present with mediastinal or hilar lymphadenopathy and parenchymal lung disease
Initial presentation may be an abnormal chest x-ray with mediastinal and hilar adenopathy
Lofgren’s syndrome?
- Acute manifestation of sarcoidosis
- Erythema nodosum- More common in women
Arthritis- More common in men - Bilateral Hilar
- Lymphadenopathy
Prognosis is favorable
sarcoidosis cxr staging?
Stage 0: Normal
Stage 1: Bilateral hilar adenopathy
Stage 2: Bilateral hilar adenopathy and parenchymal infiltrates
Stage 3: Parenchymal infiltrates without lymphadenopathy
Stage 4: Advanced parenchymal disease with fibrosis
sarcoidosis tx?
prednisone, immunosuppressives if not responsive
diseases associated with silicosis?
TB, COPD, chronic bronchitis, rheumatoid arthritis, lung cancer
Hilar adenopathy with eggshell calcification is strongly suggestive
Progressive massive fibrosis is characterized by coalescence of the nodules with larger mass lesions
Acute silicosis displays air space and interstitial pattern on x-ray
CWP?
Usually no symptoms or signs
Can have symptoms of bronchitis
May lead to progressive massive fibrosis
no associated TB or cancer, however silicosis is also common in coal workers
Caplan syndrome
rheumatoid arthritis with large cavitary pulmonary nodules associated with silicosis and coal worker’s pneumoconiosis
asbestosis
Ferruginous bodies, asbestos bodies
Symptoms
Dyspnea
Dry cough
Chest tightness/pain
Signs
Inspiratory crackles
clubbing
associated with: mesothelioma, lung cancers, pleural effusions
Chest x-ray
Pleural plaques
Pleural effusion 10-15 year latency
Pleural thickening
beryllium disease
at risk: Aerospace Electronics Ceramics Metal Nuclear
Acute Toxic Pneumonitis: high exposure can lead to a hypersensitivity response that is now rare due to better recognition of beryllium associated disease: see dyspnea, cough, c/p, blood tinged sputum, crackles
Chronic beryllium disease: clinical features are similar to sarcoidosis ranging from asymptomatic to severe granulomatous restrictive lung disease: see dyspnea, cough, c/p, w/l, fatigue, arthralgias
CXR: shows enlarged hilar/mediastinal nodes, multiple lung nodules or fibrosis, hyperinflation and honeycombing
Positive BeLPT( beryllium lymphocyte proliferation test performed on blood or BAL fluid
Usual Interstitial Pneumonia
= same as idiopathic pulmonary fibrosis (UIP is the pathologic process of IPF)
- pathogenesis unknown- BUT SEE PATCHY areas of parenchymal fibrosis and interstitial inflammation interspersed between areas of relatively preserved lung tissue
- FIBROSIS is the most prominent component of the pathology (due to collagen deposition and type II hyperplasia)
- HONEYCOMBING – cystic airspace from retraction of surrounding fibrotic tissue
Most important disorder in this category is idiopathic pulmonary fibrosis
Desquamative Interstitial pneumonia
“Smoker’s macrophages in alveoli” - see minimal fibrosis (not UIP precursor)
Pigmented macrophages in respiratory bronchioles secondary to smoking
***Smoking is believed to be an important underlying cause
- see ground glass appeaerance on imaging, lung biopsy shows macrophages with little fibrosis
- prognosis is better than IPF
- responds to corticosteroids usually and stopping smoking
Respiratory bronchiolitis - (associated interstitial lung disease)
Related to DIP- see pigmented macrophages in bronchioles full of junk!
Interstitial inflammation is not present
Almost always associated with SMOKING!
Most important intervention is smoking cessation
nonspecific interstitial pneumonia
** NOT as sick or progressive as IPF
Mononuculear cell infiltration within the alveolar walls
Uniform process
Fibrosis is variable, but less than UIP - NO HONEYCOMBING
Idiopathic or connective tissue disorder
Better prognosis - all lesions are same age
- ground glass appearance on imaging- lung biopsy shows predominantly inflammatory response in the alveolar walls , with little fibrosis
- responds to corticosteroids usually
Acute Interstitial pneumonia
** rapid onset (sx similar to ARDS), acute resp. failure following illness of interstitium filled with inflammatory cells
Organizing or fibrotic stage of alveolar damage, which is the histologic pattern seen in ARDS.
No initial trigger identified.
Histology shows fibroblast proliferation and type II pneumocyte hyperplasia in the setting of what appears to be organizing alveolar damage
Imaging with ground glass appearance
Note: this one is on its own, and is associated with rapid lung failure due to ARDS like presentation!
Cryptogenic organizing pneumonia
COP = Bronchiolitis obliterans organizing Pneomonia
Organizing fibrosis (granulation tissue) in small airways - NO HONEYCOMBING, no interstitial fibrosis, just filling up of the airways
- see cough and dysnpea
Mild degree of chronic interstitial inflammation- Intraluminal airway involvement is a key feature (see alveoli filled with fibroblasts)
Idiopathic
Differential: infections, toxic inhalants, or connective tissue disease
Chest x-ray often mimics pneumonia with one or more alveolar infiltrates
Response to steroid is dramatic and occurs over days to weeks.
idiopathic pulmonary fibrosis
= A type of usual interstitial pneumonia
- No recognizable inciting agent - unpredictable disease
- Presents between ages 50-70
- Insidious onset
Dysregulated pattern of FIBROSIS in response to alveolar epithelial injury
DYSPNEA is the most common complaint
RALES on lung examination
Patients frequently have clubbing
CXR shows bilateral diffuse interstitial pattern thats more prominent at lung bases
high resolution CT shows patchy interstitial densities and HONEYCOMBING indicative of irreversible fibrosis
prognosis is poor: 2-5 years
Rheumatoid arthritis
Primary manifestation is inflammatory joint disease
Most common site of thorax involvement is the pleura
Pleurisy, pleural effusions or both
Lung parenchymal involvement includes one or multiple nodules or the development of interstitial lung disease
Interstitial lung disease is usually mild, but can be severe in some cases
SLE
Multisystem disease that affects joints and skin
Serious organ involvement includes kidneys, lungs, nervous system, and heart
Involvement of the thorax includes pleural disease presenting with pleuritic chest pain, pleural effusion, or both
Acute pneumonitis in which infiltrates often involve the alveolar spaces as well as the alveolar walls
Less frequently chronic interstitial lung disease – extensive fibrosis usually not prominent
scleroderma “Progressive systemic sclerosis”
Pulmonary involvement tends to be severe with significant scarring of the pulmonary parenchyma
Pulmonary fibrosis strongly associated with an autoantibody to topoisomerase I (antitopoisomerase I, also called Scl70)
Pulmonary Artery Hypertension – small pulmonary vessel disease independent of the fibrosis
polymyositis-dermatomyositis
Muscles and skin are the primary sites of the inflammatory process
Interstitial lung disease is relatively infrequent
Respiratory difficulty secondary to weakness of the diaphragm
Involvement of the striated muscles in the proximal esophagus may lead to dysphagia and recurrent aspiration pneumonia
Pulmonary Langerhans Histiocytosis
- proliferation of dendritic cells in response to smoking
- Differential diagnosis of unexplained interstitial disease in the young or middle aged adult
- **Disease occurs almost exclusively in smokers
Histiocytic cell appears to be an antigen-presenting dendritic or phagocytic cell called a Langerhans cell
Cytoplasmic rod like structures called X bodies (Burbeck Granules) which can be seen by electron microscopy
Chest x-ray:
Nodular or reticulonodular disease
Upper lobe prominent
HRCT
Small cysts in addition to the nodular and reticulonodular changes
Cysts may rupture and cause pneumothorax
Some cases extensive honeycombing
Lymphangioleiomyomatosis
Characterized by proliferation of atypical smooth muscle cells around lymphatics, blood vessels, and airways, accompanied by numerous small cysts throughout the pulmonary parenchyma
Occurs almost exclusively in women of childbearing age
Develops in 30-40% of female patients with the genetic condition tuberous sclerosis complex
Clinical Manifestation
Dyspnea and cough
Vascular involvement may lead to hemoptysis
Lymphatic obstruction may produce a chylous pleural effusion
Airway involvement may lead to airflow obstruction
Rupture of subpleural cysts can lead to spontaneous pneumothorax
CXR: shows cystic changes in reticular pattern
Goodpastures syndrome
- affects lungs and kidneys: with anti-GBM antibodies against type IV collagen
plasmapheresis can be used to tx
Wegener Granulomatosis
Upper respiratory tract, lungs, and kidneys– necrotizing small-vessel granulomatous vasculitis
Chest x-ray:
Nodules, infiltrates, cavitation
Diffuse interstitial lung disease is not characteristic
cANCA + (PR3 ANCA)
Churg-Strauss Syndrome
Peripheral and lung eosinophilia
Increased immunoglobulin E levels
Systemic necrotizing vasculitis
Affects upper and lower respiratory tracts
Preceded by allergic disorders such as asthma , allergic rhinitis, sinusitis or drug reaction
CXR: shows bilateral pathy, diffuse nodular infiltrates and reticulonodular
Chronic eosinophilic pneumonia
Pulmonary interstitium and alveolar spaces are infiltrated by eosinophils and to a lesser extent macrophages
Clinical Manifestations
Occurs over weeks to months
Fever, weight loss, dyspnea, and productive cough
Increased eosinophils in the peripheral smear
BAL with increased
eosinophils
tx: corticosteroids
pulmonary alveolar proteinosis
- see cough and sputum with gelatinous yellow chunks and bilateral patchy distribution on CXR
Primary pathologic process affects the alveolar spaces, not the alveolar cells
Alveolar spaces are filled with a proteinaceous phospholipid material (acellular surfactant) that represents components of pulmonary surfactant
Clinically:
Dyspnea and cough
Bilateral alveolar infiltrates
HRCT crazy paving pattern produced by thickening of interlobular septa accompanied by ground –glass alveolar filling
Superimposed to respiratory infections - Nocardia
tx: whole-lung lavage
Hypersensitivity pneumonitis
Hyperimmune respiratory syndrome caused by inhalation of a wide variety of allergic antigens that are usually organic (see Type III and Type IV reaction - i.e. immune complex deposition and delayed response hypersensitivity — this is not a Type I where you would see IgE levels high)
suspect if: Intermittent pulmonary and systemic symptoms, associated with a certain environmental exposure
i.e. farmers, bird keepers, woodworkers, cheese makers
Farming and agriculture – especially dairy cattle
Thermophillic actinomycetes in moldy hay, grain, or silage
Ventilation/water-related contamination: Thermophillic actinomycetes
Mycobacterium avium-intracellulare complex organisms
CXR: diffuse reticulondoular, see ground glass opacities
amiodarone lung
Usually 2-4 months of treatment at doses greater than 400 mg/day, in elderly
- present with exertional dysnpnea as major problem, may mimic pulmonary infection.
- See Lipid laden foamy alveolar macrophages
- see chronic interstitial pneumonia, organising pneumonia and AIP that can even lead to ARDS
on CXR: see multiple areas of dense air space with interstitial fibrosis
what things cause increased DLCO?
diffuse alveolar hemorrhage, polycythemia
diagnostic criteria for Churg Strauss?
- Asthma
- Eosinophils greater than 10% of a differential white blood cell count
- Presence of mononeuropathy or polyneuropathy
- Non-fixed pulmonary infiltrates
- Presence of paranasal sinus abnormalities
- Histological evidence of extravascular eosinophils
Churg–Strauss syndrome (CSS, also known as eosinophilic granulomatosis with polyangiitis [EGPA] or allergic granulomatosis) is an autoimmune condition that causes inflammation of small and medium-sized blood vessels (vasculitis) in persons with a history of airway allergic hypersensitivity (atopy). It usually (but not always) manifests in three stages. The early (prodromal) stage is marked by airway inflammation; almost all patients experience asthma and/or allergic rhinitis; the second stage is characterized by abnormally high numbers of eosinophils (hypereosinophilia), which causes tissue damage, most commonly to the lungs and the digestive tract. The third and final stage consists of vasculitis, which can eventually lead to cell death and can be life-threatening.
causes of decreased DLCO?
DLCO is decreased in any condition which affects the effective alveolar surface area:
Hindrance in the alveolar wall. e.g. fibrosis, alveolitis, vasculitis
Decrease of total lung area, e.g. Restrictive lung disease
Chronic obstructive pulmonary disease (COPD), due to large residual air stuck in the lungs
Uneven spread of air in lungs, e.g. emphysema
Pulmonary embolism
Cardiac insufficiency
Pulmonary hypertension
Bleomycin (upon administration of more than 200 units)
Chronic heart failure[4]
Anemia-due to decrease in blood volume
Amiodarone high cumulative dose; more than 400 milligrams per day
criteria for exudate?
- Pleural fluid protein/serum protein > 0.5
- Pleural fluid LDH/Serum LDH > 0.6
- Pleural fluid LDH more than two-thirds normal upper limit for serum
Heerfordt’s Disease
A variant of Sarcoidosis
Characterized by nonsuppurative parotitis, uveitis, mild fever, and facial nerve paralysis
IPF immunology?
- restrictive pattern of fibrosing
- corticosteroids not indicated (though are useful in nonspecific interstitial pneumonia)
- see fibroblast proliferation and deposition of fibrin
injury to lung –>increased TGFbeta –> Type II AEC proliferates
injury to lung –> vasodilation/coagulation/vascular remodeling –> Type II AEC proliferation
- there is evidence of cellular and humoral immunity in IPF: CD4 T cells and autoantibodies
Genetic contribution: telomerase mutations, MUC5B mutations
sarcoidosis immunology?
- multisystemic noncaseating epithelioid granulomas
- can progress to fibrosis with loss of alveolar and bronchial tissue and vascular surface area
** see increase in TNFalpha, IL7, MMP12 - T cells surround granulomas full of macrophages
Hypersensitivity Pneumonitis immunology?
- due to inhalation of exogenous organic material
- see transient fever, hypoxemia, myalgias, arthrlagias, dyspnea, cough - sx resolve w/out tx provided there isn’t rexposure to ag
- ex: Bird Breeder’s lung
- in course of exposure: around 4-12 hours see decreased VC and DLCO2, that resolves in 24 hours after exposure
- this is not associated with IgE or eosinophils
- higher prevalence in smokers
- lymphocytosis is common
*** see increased TGFbeta, IL1, IL12, TNFalpha, IL2, IFNgamma, IL6, IL17, IL22
- if persistant –> fibrosis
tx with corticosteroids aids recovery initially
presence of Eosinophils in BAL?
eosinophilic lung disease - see infiltration in airways, alveoli, or interstitium
wheeze
a continuous musical sound that is generated by flow through critically narrowed collapsible bronchi - this is heard in asthma, COPD, pulmonary edema, bronchiolitis, bronchiectasis
what do restrictive vs. obstructive diseases show?
R: decreased VC, decreased TLC, RV, FRC
O: decreased VC, increased TLC,RV, FRC
mild intermittent asthma?
sx presents less than 2 days per week, or less than 2 nights per month
tx: SABA as needed
mild persistent asthma?
sx present more than 2 days per week - but less than once daily
tx: SABA as needed, inhaled corticosteroid or montelukast
moderate persistent asthma?
sx are daily or more than once per night
tx: SABA as needed, low/medium dose corticosteroid, LABA
severe persistent asthma?
sx are continual during the day and freq. at night
tx: SABA as needed, high dose corticosteroid, LABA
centriacinar emphysema
affects resp. bronchioles distal to terminal bronchiole - occurs w/ smoking
panacinar emphysema
affects alveolar ducts, alveoli and coalesce to form bullae - occurs with alpha1 antitrypsin deficiency and with lots of smoking
what causes emphysema
imbalance of elastase-antielastase in lung
nodular pattern in upper lobes? eggshell calcifications?
Silicosis - seen with mining/sandblasting
- increased risk of TB, COPD, lung cancer, bronchitis
ferruginous bodies?
asbestosis
signs of asbestosis?
dyspnea, dry cough, c/p
insipratory basal crackles/clubbing
mesothelioma, lung cancer, pleural effusion and pleural plaques
which disease is similar to sarcoidosis? see granulomatous restrictive lung disease, dyspnea, cough, c/p, w/l, fatigue, arthralgias? enlarged hilar lymph nodes, fibrosis
beryllium exposure disease - think aeronautics, electronics, ceramics
infectious etiologies leading to bronchiectasis? genetic etiologies? Immune etiologies?
childhood pertussis
TB
MAI (mycobacterium avium intracellular) - involves the right middle lobe and lingula
genetic: CF, ciliary dyskinesia, alpha1at
Immune: hypogammaglobulinemia, IgG defciency, HIV, Sjogren’s syndrome, RA
upper lobe bronchiectasis? lower lobe? right middle lobe? central?
upper: CF
lower: aspiration
right middle: MAI
central: allergic bronchopulmonary aspergillosis
tx for sarcoidosis?
prednisone for 3 mos
p-anca and IgE elevated along with BUN and creatinine - CXR shows bilateral patchy infiltrates - has asthma and allergies and now has neuritis and maculopapules with marked abdominal pain?
churg- strauss syndrome
charcot-leyden crystals? curschmann spiral?
all indicators of asthma - see eosinophils in the serum
what drug used to treat rheumatoid arthritis can cause lung disease?
methotrexate lung disease: see SOB, cough, fever
- can result in fibrotic inflammatory disease, pulmonary infections or AIP
- CT shows diffuse parenchymal opacification and reticular opacities
- NSIP is the most common presentation
