restrictive lung disease Flashcards
1
Q
Using HRCT (High-resolution computed tomography) to Diagnose IPF
A
- UIP RADIOGRAPHIC Pattern: Typical features of UIP need be present on HRCT and atypical features absent to make confident diagnosis of IPF/UIP [UIP = usual interstitial pneumonia]
Characteristic Features:
- Irregular reticular lines (diffuse)
- Subpleural, posterior, and lower-lobe predominance
- Subpleural honeycombing
- Minimal ground glass opacities
- Traction bronchiectasis (occurs later in disease course)
- Loss of normal lung architecture/distortion
- Patchy involvement of the lung (heterogeneity)
- Peripheral zones of chronic scar and honeycomb change predominate
- Fibroblast foci present at junction of normal lung and fibrotic change
- Interstitial inflammatory change is usually only mild and focal
2
Q
A
Siliconic nodules x ray
3
Q
Common Risk Factors for ARDS
A
Direct
- Pneumonia
- Aspiration
- Inhalational Injury
- Pulmonary Contusion
- Pulmonary Vasculitis
- Drowning
Indirect
- Non-pulmonary sepsis
- Major Trauma
- Pancreatitis
- Severe Burns
- Non-cardiogenic shock
- Drug Overdose
- Transfusion related acute lung injury (TRALI)
4
Q
Diagnosis of IPF
A
- Gradual onset
- Age 50+ (rarely seen in younger individuals)
- Exclusion of other known causes of interstitial lung disease including drug toxicities, environmental exposures, and collagen vascular diseases
- Exam usually shows inspiratory crackles (or rales) and clubbed digits
- High-resolution computed tomography (HRCT) scans show Usual Interstitial Pneumonia (UIP) radiographic pattern
- PFTs show restriction, reduction in DLCO, and exertional desaturation
- Surgical Lung Biopsy showing Usual Interstitial Pneumonia (UIP) pathologic pattern
5
Q
Pathophysiology of ARDS
A
- Acute respiratory distress syndrome (ARDS) is an acute lung injury due to an inciting event causing complement activation and subsequent lung damage, leading to refractory hypoxemia.
- Initial Injury to capillary Endothelium and/or alveolar epithelium
- Results in leaky alveolar capillary units
- Elaboration of protein-rich, cell-rich exudates into the alveolar space.
6
Q
Pathology of Hypersensitivity Pneumonitis
A
- Poorly formed (loose) granulomas that are centered around small airways (bronchioles)
- Multinucleated Giant Cells
- Diffuse mixed interstitial inflammation
7
Q
What is Silicosis
A
- a slowly progressing nodular, fibrosing pneumoconiosis that is caused by inhalation of pro-inflammatory silicon dioxide (a component of many types of stone). Silicosis is currently the most prevalent occupational disease worldwide
- Chronic bouts of inflammation and resolution are the main cause of the slowly progressive nodular fibrosis
8
Q
Pathogenesis of Fibrosis in Idiopathic Pulmonary Fibrosis
A
9
Q
Pulmonary Edema triggered by:
A
- Increased hydrostatic force (cardiogenic pulmonary edema)
- Damage to the alveolar-capillary barrier (ARDS)
- Lymphatic obstruction
10
Q
Classification of Interstitial Lung Diseases (chart visualization)
A
11
Q
Pulmonary function tests of hypersensitivity pneumonitis
A
- Important to establish severity and progression
- Mixed obstructive/restrictive pattern can be found
- Isolated elevated RV
- Disproportionately low flows (FVC and FEV1)
- Low FEV1/FVC
- Most common: isolated restriction
- Summary: some patients just have restrictive patterns, some patients have both obstructive and restrictive
- The mix of obstructive and restrictive indication is unique to HP
12
Q
Etiologies of Restrictive Lung Disease: Extrapulmonary Causes and Pulmonary Causes
A
13
Q
ARDS: Acute Respiratory Distress Syndrome
A
- Referred to as the lower pressure pulmonary edema
- Syndrome of acute respiratory failure characterized by:
- Injury and disruption of the alveolar-capillary membrane
- Alveolar flooding with protein-rich edema fluid (exudative)
- Severe hypoxemia
- Reduced lung compliance
- Acute: Within one week of a known clinical insult or new or worsening respiratory sxs
- Bilateral pulmonary infiltrates on CXR or CT
- Non-cardiac: pulmonary edema not fully explained by cardiac failure or fluid overload
- need objective assessment (echo) if no risk factor present
- Hypoxemia
- P:F ≤ 300 (where P=PaO2 and F=FiO2) on PEEP ≥5 cmH20
- Mild (200-300); Moderate (100-200); Severe (<100)
14
Q
Asbestos-Related Malignancy
A
- Malignant Mesothelioma
- Smoking does NOT increase the risk of mesothelioma in asbestos workers
- malignant tumor of the visceral or parietal pleura that results from long term exposure to asbestos
- Primary Lung Cancer
- Smoking greatly increases the risk of lung cancer in patients exposed to asbestos
- No preferential pathologic subtype
15
Q
Acute Exacerbation of IPF
A
- Acute shortness of breath
- New radiographic infiltrate
- Worsening gas exchange
- No evidence of other cause: – Infection – Heart failure – Thromboembolism – Pneumothorax
16
Q
Asbestosis
A
- Asbestosis is a pneumoconiosis associated with the inhalation of asbestos particle
- Asbestos fibers are persistent (not able to be cleared) and biologically active, and may lead to the generation of oxygen free radicals, which is injurious to the local tissue
- Results in slowly progressive fibrosis of the lung.
- Due to long latency between exposure and disease onset (>20 years), age-adjusted mortality of asbestosis continues to increase in US
- Concomitant tobacco abuse is common.
- The earliest symptom of asbestosis is typically dyspnea with exertion.
- Bibasilar Fine Crackles on lung exam, clubbing
- Restriction on PFTs
17
Q
Imaging in Chronic Hypersensitivity Pneumonitis
A
- Upper lobe predominance:
- Diffuse bilateral reticulo-nodular pattern (lines and dots)
- Ground-glass opacities
- Areas of Air-trapping (mosaicism)
18
Q
Lung Biopsy in Asbestosis
A
- The presence of ferruginous bodies in lung tissue strongly suggests asbestos-related pulmonary disease. They arise from the coating of inorganic particulates with an iron-containing proteinaceous material. They microscopically appear as golden colored rods, because they have become coated with ferruginous (iron rich) protein rich material following phagocytosis by tissue macrophages.
- strong indicator of abestos, but hard to find so not required for diagnosis
19
Q
Chest CT in Asbestosis
A
- Peripheral and basilar interstitial fibrosis and honeycombing
- can be identical to UIP pattern of fibrosis
- Pleural plaque – Calcification of the pleura as well as the domes of the diaphragm can occur, forming “pleural plaques.
20
Q
the most common manifestation from asbestos exposure
A
Pleural plaques
21
Q
How cardiogenic pulmonary edema causes restrictive lung disease
A
- Decreased compliance:
- Interstitial water
- Flooded alveolar units (loss of participation in ventilation)
- Hypoxemia
- Activation of alveolar stretch receptors (J receptors)
- Nerve endings in alveolar walls next to capillaries (Vagal nerve afferent)
- Responsive to increases in interstitial fluid
- Leads to simulation of ventilation (increased respiratory rate)
22
Q
Common Clinical Findings in Interstitial Lung Diseases
A
- Dyspnea on exertion (due to increased work of breathing)
- Fatigue
- Non-productive (paroxysmal) cough
- Abnormal breath sounds to auscultation
- Abnormal CXR/CT (interstitial opacities)
- Hypoxemia (first with exercise/ambulation)
- Clubbing
23
Q
Common Interstitial Lung Diseases
A
- Idiopathic pulmonary fibrosis
- Asbestosis
- Silicosis
- Hypersensitivity Pneumonitis
24
Q
Hypersensitivity Pneumonitis (HP) (Extrinsic Allergic Alveolitis)
A
- Hypersensitivity pneumonitis is caused by chronic high-level exposure to inhaled irritants
- Lung disease resulting from recurrent exposures to organic particles
- Susceptible subjects are sensitized to the inciting antigen, and develop bronchiolocentric granulomatous lymphocytic infiltrates
- Bronchiolocentric –inflammation centered around terminal bronchioles
- Acute or chronic
25
Q
Etiologies of Lung Inflammation
A
- Autoimmune (lupus, scleroderma, rheumatoid arthritis)
- Injury (aspiration, noxious inhalation, trauma)
- Medications (methotrexate, bleomycin, nitrofurantoin, amioadarone, etc)
- Hypersensitivity pneumonitis (moldy hay, hot tubs, birds, water damage/molds)
26
Q
Management of ARDS
A
- Protecting lung from further injury – “Lung protective ventilator strategy”
- Addressing shunt
- Deliver positive and re
- Low tidal volumes (4-6cc/kg ideal BW)
- Permissive hypercapnea (pH ≥ 7.20)
- Limit alveolar distending pressure (≤30 cmH2O)
- Non-toxic FiO2 (≤0.60)
- Positive end-expiratory pressure to recruit (open-up) flooded/collapsed alveolar units
27
Q
Pneumoconioses
A
- Definition: “the accumulation of dust in the lungs and the tissue reactions to its presence”
- Tissue reactions (severity is related to total dust burden): Nodular fibrosis and Diffuse fibrosis
- Dusts of concern:
- Asbestos
- Silica
- Coal
- Dust
- Talc
- Mica
- Hard Metal (Silicon Carbide)
- Beryllium
28
Q
A
Asbestos induced pleural plaques
29
Q
Pathophysiology of Silicosis
A
- Inhaled crystalline particles are engulfed by alveolar macrophages. Phagocytosed silica causes activation of those macrophages, and promotes the release of inflammatory mediators such as IL-1, TNF, and the formation of free radicals.
- Inside those macrophages, engulfed silica also impairs phagolysosome formation, leading to an increased risk of infection/exacerbation of infection with intracellular bacteria.
- An increased susceptibility to M. tuberculosis (an intracellular bacteria) infection or exacerbation of an ongoing or latent M. tuberculosisinfection is an especially feared complication of silicosis
30
Q
A
Progressive Massive Fibrosis
31
Q
Asbestos-related (benign) pleural diseases
A
Benign asbestos pleural effusion (BAPE)
- Shortest latency period to disease presentation
- Termed benign, as it occurs in the absence of mesothelioma
- Usually unilateral, and often bloody and eosinophilic
- Thought to be a reaction to asbestos fibers in pleural space • Typically resolves
- Tends to go away on its own
Hyaline pleural plaques
- Most common CXR abnormality in asbestos-exposed pts
- (in 20-60% of patients with significant exposure)
- Usually asymptomatic
- Discrete areas of fibrosis/thickening of parietal pleura
- Does not progress to malignant melanoma
Rounded atelectasis secondary to pleural adhesions
- Usually asymptomatic
- “Comet-tail” sign on chest CT
32
Q
Resolution phase of ARDS
A
- Full re-epithelialization (differentiation into type I AECs)
- Endothelial restoration
- (partial) resolution of scar formation
33
Q
A
Hypersensitivity Pneumonitis
34
Q
Cardiogenic pulmonary edema
A
- Cardiogenic (hydrostatic or high pressure) pulmonary edema
- Rising capillary hydrostatic forces:
- Increase in interstitial edema
- Overwhelms lymphatic drainage
- Development of alveolar edema
- Fluid is transudative (low protein, low cells)
35
Q
ARDS leading to restrictive lung disease
A
Reduced lung compliance
- flooded alveolar units
- collapsed alveolar units
- Surfactant dysfunction from inactivation from plasma protein leak and decreased production (type II cell injury)
- interstitial edema/inflammation
Acutely, leads to severe restrictive lung disease
- Difficult to inflate/ventilate
- Loss of ventilated alveoli leads to risk of over-distension and barotrauma
36
Q
Idiopathic Pulmonary Fibrosis (IPF)
A
The most common form of idiopathic interstitial pneumonia
- Idiopathic Pulmonary Fibrosis = Clinical Condition
- Usual Interstitial Pneumonia = Pathologic (or radiologic) pattern seen in IPF
- Increasing incidence and prevalence (34K new dx/yr, 89k total US)
- Disease of aging; Usually occurs after fifth decade of life (highest in the elderly)
- Dismal prognosis; Median survival is approximately 3-4 years post-diagnosis
- Immunosuppressive medications are harmful
- Pirfenidone (anti-TGF-β) and Nintedanib (small molecule inhibitor of VEGF-R, EGFR, and FGF-R tyrosine kinases) now approved for use in this condition
37
Q
Asbestos
A
- Fibrous, naturally occurring mineral, which possesses qualities of heat resistance, and can be spun.
- Used in pottery and clothing (fire resistant) dating back to 2500 B.C.
- In the industrial age, asbestos was used for in a wide variety of applications with the most common insulation, fire-proofing, and friction materials
- Asbestos-related lung disease is directly caused by inhalation of the fibers
- Phagocytosis of fibers
- direct cell cytotoxic effects
38
Q
pathogenesis of asbestosis
A
mediated by macrophages within the lung tissue
- Pulmonary macrophages attempt phagocytosis of asbestos fibers.
- Within macrophages, asbestos fibers induce the release of chemotactic factors and inflammatory mediators, ultimately leading to pulmonary inflammation and fibrosis
39
Q
Disease Manifestations of Acute vs. Chronic Silicosis
A
Acute – Dyspnea, cough, fatigue Alveolar filling with protein/cell rich exudate (similar to pulmonary alveolar proteinosis)
Chronic – Upper lobe nodules; Egg-shell calcifications of mediastinal lymph nodes
40
Q
Treatment of silicosis
A
- No proven therapies to prevent progression
- Avoidance of further exposure
- Tobacco cessation
41
Q
[P:F Ratio]
A
- Ratio of arterial oxygen tension to the concentration of inspired oxygen (PaO2/FiO2)
- FiO2 is expressed as a fraction of 1 (i.e. 60% = 0.6)
- PaO2 112 in patient receiving FiO2 40% is a P:F ratio of 280 (112/0.4)
- Lower P:F means worse oxygenation
42
Q
Diagnosis of Asbestosis
A
- Take and document a reliable exposure history to asbestosis fibers
- Need appropriate latency period (>20 yrs)
- Evidence of interstitial lung fibrosis
- Crackles on lung exam
- Typical chest radiograph or chest CT
- For legal cases a certified B-reader is required to score a chest radiograph
- Absence of other causes
- Histology – Sub-pleural pulmonary fibrosis is the primary gross histopathologic finding in asbestosis
43
Q
What is Pneumonia
A
- Infection in the pulmonary parenchyma.
- Initiates an inflammatory response
- Neutrophilic infiltration into alveolar airspaces
- Localized capillary leak and the formation of intraalveolar exudates
44
Q
Symptoms of ARDS include:
A
- acute dyspnea
- cyanosis
- tachypnea
- wheezing
- rales and rhonchi
45
Q
Hypersensitivity Pneumonitis – Chronic HP
A
- Chronic, repetitive small exposures
- Indolent presentation, with dyspnea on exertion (indolent – causing little or no pain)
- Cough, crackles, inspiratory squeaks
- Some pts have evidence of fibrosis on chest CT
- Poorer prognosis; some have progressive, irreversible disease; Can have stabilization
46
Q
A
Calcified lymph nodes (egg-shell calcification)
47
Q
Diagnosis of Hypersensitivity Pneumonitis
A
- Known exposure to inciting antigen: – History – Environmental investigation – Serologic evidence (IgG against antigen – indicates sensitization)
- Compatible clinical findings – Crackles, cough, SOB, wheeze, fatigue, fever, weight loss associated with antigen exposure – Chest radiograph/CT – reticular/nodular/ground-glass opacities
- Bronchoalveolar lavage with lymphocytosis (>20%) or biopsy
- Positive inhalation challenge – Improvement with removal from environment, worsening with re-exposure to the environment – Inhalation challenge (PFT) to the suspected antigen
- Histopathology: – Most often requires a surgical lung biopsy – Poorly formed, non-caseating granulomas – Mononuclear cell infiltrate
Definite HP = 1,2,3 OR 1,2,4 OR 2,3,5
48
Q
In silicosis, chronic exposure results in a local-tissue reaction in:
A
- Lung (upper lung nodules)
- mediastinal lymph nodes (egg-shell calcifications)
49
Q
Management of Idiopathic pulmonary fibrosis
A
- Establish an accurate diagnosis (usually requires referral to a tertiary care center specializing in ILD
- Pirfenidone and Nintedanib-Inhibit fibrogenic pathways
- Pulmonary rehabilitation
- Supplemental oxygen
- Clinical trials of investigational agents for willing and eligible patients
- Lung transplantation for eligible patients
- Relief of dyspnea/palliative care/hospice
50
Q
Treatment of Hypersensitivity Pneumonitis
A
- Identification and avoidance of exposure
- Corticosteroids for subacute or severe acute
- Consideration of steroid-sparing agents (mycophenolate mofetil, azathioprine, rituximab) for progressive disease
- Lung transplant evaluation
51
Q
A
Rounded Atelectasis
52
Q
Dyspnea in silicosis
A
only seen late in the progression of the disease and after substantial fibrosis has occurred. Long term morbidity is due to progressive respiratory impairment
53
Q
Remember causes of ARDS with the mnemonic ARDS (AAAARDDDSSS):
A
- Aspiration
- Acute pancreatitis
- Air or Amniotic embolism
- Radiation
- Drug overdose
- DIC
- Drowning
- Shock
- Sepsis
- Smoke inhalation
54
Q
A
Silicotic Nodules
55
Q
gross pathological examination of silicosis
A
- silicosis appears as tiny pale nodules commonly seen in the upper zones of the lung. As the disease progresses, the nodules turn into hard collagen-dense scars.
56
Q
Often first clinical presentation of prior asbestos exposure
A
Benign Asbestos Pleural effusion (BAPE)
57
Q
Compliance curves of restrictive lung disease
A
Restriction due to lung disease (lungs are more stiff)
- Compliance curve of lung compliance will drop
- The sum of the chest and lung compliances will also then drop
- This means that at any given pressure the lung volume will be less
Restriction due to chest wall
- If chest wall is less compliant then the sum compliance curve will more to the run
- At any given pressure the lung volumes will be less
Restriction due to weakness
- Has to do with how much strength we can generate
- Patient has a maximal inspiratory pressure that they can reach that’s lower than a healthy person – compliance curve only goes up to a max pressure (maximum on x-axis) that leads to a max volume that can be reached following on the curve
58
Q
Arterial Blood Gas in ARDS
A
- Low arterial oxygen tension (i.e low Pa02)
- Much higher alveolar oxygen tension (PAO2) than arterial oxygen tension(PaO2) – high A-a gradient
- Slight respiratory alkalosis (low PCO2, high pH) due to stimulation of ventilation by hypoxemia and stimulation of J receptors
59
Q
Restrictive lung disease
A
- disruption in balance of elastic forces and transpulmonary pressures leading to smaller volumes
- A reduction in total lung capacity (TLC) on PFTs is required to make the diagnosis
Caused by:
- Lung diseases that result in decreased compliance, resulting in decreased lung volumes
- Extrapulmonary restriction (chest wall, respiratory muscle strength, pleura) that limits the ability to generate negative pleural pressure
60
Q
Acute Hypoxemic Respiratory Failure
A
- severe arterial hypoxemia that is refractory to supplemental O2. It is caused by intrapulmonary shunting of blood resulting from airspace filling or collapse. Findings include dyspnea and tachypnea.
- Physiology
- airspace flooding: edema, pus, blood in alveoli
- Intrapulmonary shunt physiology (Qs/Qt)
- Hypoxia is refractory to oxygen supplementation – oxygen supplementation doesn’t help much
61
Q
Interstitial Lung Diseases: overview and common pathophysiology
A
Overview
- Disorders predominately affecting the interstitial space of the lung
- Primarily (but not exclusively) affects the lung parenchyma (alveolar/capillary units) with variable patterns and degrees of inflammation, fibrosis, architectural distortion
Common Pathophysiology
- Accumulation of inflammation and connective tissue in the alveolar interstitial spaces of the lung leading to:
- Increased elastic recoil of the lung -> Restrictive lung physiology (low TLC, FRC, RV)
- Increases work of breathing
- Destruction of alveolar/capillary gas exchanging surfaces and resultant low DLCO, high A-a gradient
- Thickening of the alveolar/capillary interface -> diffusion limitation
- exercise-induced hypoxemia
62
Q
Asbestos Enviromental Exposure
A
- Plumbing, insulators, Sheet metal
- Shipbuilding
- Brake workers
- Dockworkers
- Remodeling, demolition
- Milling, mining
- Soils, Turkey, Albania
63
Q
Presentation of lung inflammation (restrictive lung disease)
A
- Widened alveolar septa
- Increased elastic recoil forces
- Increased work of breathing
- Loss of alveolar/capillary units
- Hypoxemia
64
Q
Environmental exposures of silicosis
A
mining, sand blasting, ceramics, metal casting
65
Q
Chronic Phase of ARDS
A
- “Fibroproliferative Phase”
- Fibroblast proliferation and collagen deposition in areas of injury (scarring)
- Type II epithelial cell proliferation (re-epithelialization)
- Initiation of resorption of the exudate
66
Q
Diffuse Alveolar Damage (DAD) in ARDS
A
- Alveolar septal thickening (edema/inflammatory cells)
- Hyaline membranes
- Proteinacious deposits in alveolar spaces
- Results from fibrin-rich exudative edema fluid and remnants of necrotic epithelial cells
- Type II cell hyperplasia
- Attempt at repair
67
Q
Hypersensitivity Pneumonitis – Acute HP
A
- Relatively rare presentation
- Associated with a large exposure to antigen
- Mediated by immune complex deposition
- Fevers, chills, muscle aches, cough, dyspnea a few hours after exposure
- Occasionally fine crackles
68
Q
Pulmonary function tests of silicosis
A
will be normal or only slightly impaired in the early and middle stages of disease
69
Q
Common examples of hypersensitivity pneumonitis and associated exposures include
A
- Farmer’s lung: exposure to inhaled mold dusts containing thermophilic actinomycetes spores
- Pigeon breeders lung exposure to antigenic bird feathers, droppings, sera
- Humidifier (“air conditioner”) lung: exposure to thermophilic bacteria in heated water
70
Q
Clubbing in ILD
A
- Commonly seen in IPF, asbestosis, along with lung cancer, cystic fibrosis
- Can be seen, but less common in COPD and other lung conditions
- Likely develops in response to growth factors such as VEGF, PDGF
71
Q
Malignant Mesothelioma: overview, symptoms, requirement for diagnosis, chest xray, prognosis
A
- Mesothelioma is a malignant tumor of the visceral or parietal pleura that results from long term exposure to asbestos
- Smoking does NOT increase the risk of mesothelioma in asbestos workers. This is in contrast to the synergistic effect of smoking and asbestos exposure on developing primary bronchogenic lung carcinoma.
- Rare tumor arising from pleural or parietal mesothelium
- Forms a pleural mass or “rind”, often with associated effusion
- The most common presenting symptoms of mesothelioma are chest pain, dyspnea, and recurrent idiopathic pleural effusions.
- Diagnosis of malignant mesothelioma requires tissue biopsy.
- Chest x-ray will show pleural thickening and possibly pleural effusion.
- Malignant mesothelioma has a poor prognosis. Mean survival time is approximately 12 months.
72
Q
Lab findings consistent with ARDS include:
A
- Respiratory alkalosis
- Decreased O2
- Decreased CO2
73
Q
How pneumonia causes restrictive lung disease
A
Lower compliance of the lung due to:
- Loss of aerated lung (cellular and protein-rich exudate)
- Atelectatic units
- Flooded alveolar units means fewer alveolar units participate in ventilation
- Also leads to hypoxemia
74
Q
Asbestos-Related Thoracic Disease
A
- Asbestosis = ILD from asbestos exposure
- Pleural Disease (often first manifestation of asbestos-related lung disease)
- Pleural Plaques (most common 20-60% of exposed workers)
- Benign Asbestos Pleural Effusion (BAPE)
- Rounded Atelectasis
- Malignant mesothelioma
- Bronchogenic carcinoma
- Asbestosis + Smoking
75
Q
Restrictive Lung Disease: results of TLC, RV, and DLCO for reduced compliance in chest wall, lung parenchyma, and muscle weakness
A
