ILD (Raf) Flashcards
16 year old girl with SOB, inspiratory stridor, hoarsness, nasal congestion. Multiple ED visits. Labelled as asthma and VCD. (case was eventually diagnosed by findings on bronchoscopy)
GPA
(important to include GPA on differential for stridor). Pulmonary involvement is present in 80% of cases. May or may not have more obvious symptoms like pulmonary renal syndrome.
Antibody involved with GPA?
C-anca (PR3). is the primary antibody.
Some patients are MPO (p-anca)
Antibody invovled with microscopic polyangitis?
MPO (p-anca)
Pulmonary manifestations of GPA?
Upper airway: tracheal stenosis, subglottic stenosis, epistaxis, nasal septal ulceration, sinusitis, oral ulcers
Nodules (which can be caseating), look like nodules on chest imaging
Diffuse alveolar hemorrhage
Down syndrome patient with wheeze. What is your differential diagnosis?
Atopy is NOT more common in patients with Down’s compared to general population. In fact, DS patients have LOWER rates of atopy.
You should think of other things first:
- Airway malacia - could be intrathoracic or upper airway. Hypotonia could make this worse
- Vascular malformation (I don’t think they necessarily have a predisposition to vascular malformation, but need to think about broader differential for wheeze)
Why are LRTIs a big deal in patients with down syndrome?
- Can be predisposed to LRTIs because of: upper airway abnormalities, GERD (which affect airway clearance and soil the airway) + immune system abnormalities (problems with innate and adaptive immunity - lower function of neutrophil, lower antibody response to vaccines, including respiratory pathogens)
- LRTIs can be more severe since they low respiratory reserve (lower surface of lung) b/c of acinar hypoplasia, alveolar hypoplasia
- Higher chance of hospitalization, ICU, longer length of stay
2 year old DS patient with pleural effusion. Differential?
DS patients can be prone to chylous effusion inherently b/c of DS, though that’s more common in neonatal period. In an older DS child, would be improtant to think about other causes:
- infectious
- malignancy (since they are also prone to malignancy)
- pericardial effusion can be associated with hypothyroidism
For a DS neonate with chylothorax, you would definitely do full work up, but interestingly, congenital pulmonary lymphangiectasia is are in DS. (That being said, I think we had a patient with this)
Why are DS patients prone to pulmonary hypertension?
Intrinsic abnormalities of vascular bed: persistence of fetal double capillary layer, thickened pulmonary arterioles, reduced size of vascular bed (along with alveolar hypoplasia) + exacerbating factors such as OSA (also infection, aspiration)
Lower respiratory abnormalities in DS patient?
- Acinar and alveolar hypoplasia
- Subpleural cyst
- Increased prevalence of CHILD
- chylothorax
- increased frequency and severity of LRTI
- pulmonary hypertension
Upper respiratory abnormalities in DS patient?
- Narrowing of whole airway, both above and below the cords
- Above vocal cords:
* Macroglossia - I think this is relative to skeletal size * Midface hypoplasia * Narrow nasopharynx * choanal stenosis * Enlarged tonsils and adenoids - relative skeletal * Short palate
* Below the vocal cords: * Trachea is narrower by 2 mm compared to non-DS—>high incidence of post intubation stridor * Tracheomalacia:
* Tracheobronchomalacia is common * Laryngomalacia is common * Tracheal bronchus is slightly more common * Subglottic stenosis is more common—commonly related to previous intubation, though not always * Tracheal stenosis:
* Associated with vascular rings and hypoplasia of aortic arch * Tracheal versus sublottic stenosis: just differ by location of stenosis. Sublottic is right below the cords. Tracheal is a bit further down. * Symptoms of upper respiratory:
* Snoring—>important to specifically ask about this, since parents may not volunteer this info * Noisy breathing * Cough
For NEHI, what is the appearance on biopsy and staining pattern?
bombesin positive neuroendocrine cells are seen in the distal airways (respiratory bronchiole) and they can also be in clusters in alveolar duct
Imaging findings in NEHI?
- ground glass opacities centrally, in RML and lingula
- Inspiratory/expiratory CT: air-trapping
- CT is very specific (about 100%), but imperfect sensitivity at 80%
- classic CT findings are enough to make diagnosis and don’t need to go on to biopsy
what is a hydrocarbon?
What are hydrocarbons?
* Petroleum solvents * Household cleaning products * Kerosene * Liquid polishes and waxes * Furniture polish * Typical age group for accidental ingestion: * Toddlers * Age <5 years * Often these products are stored in containers that look like beverage containers
How do hydrocarbons cause lung damage?
- Lung injury is through DIRECT aspiration
- Hypoxia is the MAIN issue, as opposed to hypercapnia. This is due to:
- Surfactant inactivation—>atelectasis and V/Q mismatch
- Bronchospasm
- Hydrocarbon vapours will displace alveolar gas
What type of lung damage do hydrocarbons cause?
- Autopsy samples in humans have shown:
- Necrosis of bronchi, bronchioles and alveolar tissue
- Hemorrhagic pulmonary edema
- Interstitial inflammation
- Thromboses
What is a non-infectious cause of pneumatoceles?
Hydrocarbon aspiration
Long term complication of hydrocarbon aspiration?
Peripheral small airway disease–>obstruction with low FEV1, air trapping so high RV/TLC
No increased bronchial reactivity
What features of hydrocarbons enable them to cause lung damage?
Hydrocarbons are vicious b/c:
- Low surface tension—>spread through tracheobronchial tree
- Low viscosity—>can go deep into lung
- High volatility—>high level of blood stream absorption, which causes CNS effects
Which surfactant disorders can have a delayed presentation?
- ABCA3
- Surfactant protein C
Lamellar body in SP-B?
Disorganized with large whirls and vaculoar inclusions.
Looks like a hole with inclusions, as opposed to a tree trunk
Lamellar body in ABCA3?
-small and dense
- eccentrically placed inclusions
Fried egg (yolk and surrounding white of the egg)
Treatment for ABCA3 and SP-C?
Streoids, hydroxychloroquine, azithromyci
Which diseases cause non-caseating granulomas?
- Hypersensitivity pneumonitis
- Sarcoid
- Kendig’s also mentions: CGD, fungal, ulcerative colitis, GPA, berylliosis–>so I think some of these causes can give both caseating and non-caseating
Which disease cause caseating granulomas?
- TB
- Granuomatosis with polyangitis
- IBD (necrobiotic nodules)
Pathology findings in HP?
- Alveolitis
- Giant cells
- Foamy alveolar macrophages
- Non-caseating granulomas
4 airway manifestations of SLE
- pleuritis with pleural effusion**
- pulmonary embolus**
- acute pneumonitis**
- infection such as pseudomonas, PJP, CMV–>very important to rule out infection for pulmonary presentations of lupus **
- shrinking lung syndrome
- chronic ILD
- pulmonary hemorrhage - possible, but less common
(when practically seeing a lupus patient, also need to think about: drug toxicity, cardiac disease and renal disease which may be affecting pulmonary status)
Is routine CT for asymptomatic patients with lupus recommended?
No
Risk factors for acute chest syndrome
- Age, in particular 2-4 years of age, though pediatrics>adults
- Pulmonary infection, such as atypicals like mycoplasma
- lower HbF
- HbSS has more ACS than HbSC
- Asian haplotype
- Fat embolism
- Post op atelectasis
- Bronchospasm
- Higher WBC count
What is the biggest risk factor for sickle cell chronic lung disease?
- ACS
What is the relationship between asthma and sickle cell disease complications?
- Asthma and wheezing are independently associated with SCD complications
- ONLY wheezing is associated with ACS
What is ACS?
It's not a disease, but it's a syndrome of respiratory symptoms (fever, cough, dyspnea, hemoptysis) + new radiographic infiltrate in a patient with sickle cell. Variety of causes: - infectious - eg. mycoplasma - atelectasis - eg. post op - fat embolism
What type of lung disease is sickle cell chronic lung disease?
- fibrotic (interstitial fibrosis), difuse
- restrictive lung disease
Why are sickle cell disease at risk for OSA?
- functional asplenia—>compensatory T+A hypertrophy and extra medullary hematopoiesis
Sickle cell disease patient with obstruction, but no BD response. Etiology?
Consider causes for fixed airway obstruction, but can also have obstruction in sickle cell due to increased pulmonary capillary blood volume.
In sickle cell patients with suspected hypoxemia, how should this be confirmed?
Poor correlation between SpO2 and arterial blood gas, so should get PaO2 (blood gas)
What are signs of severe acute chest syndrome?
- Multilobar disease
- increased hypoxia
- increased RR
- low platelets
Which drug is strongly not recommended for PH management in sickle cell disease patient?
- phosphodiesterase inhibitors
Sickle cell patient with wheezing. Approach to investigation?
- PFT with pre/post bronchodilator testing
- Airway hyper-reactivity challenge tests, such as with exercise or cold air
- Methacholine challenge is NOT advised since this can cause ACS
- Key point: wheezing in SCD patient should NOT be labelled as asthma right away since there “other causes” (Kendig’s doesn’t go into details, but presumably the SCD itself with changes in pulmonary blood volume). That being said, may have lower threshold for treating for possible asthma since wheezing is a risk factor for ACS and both wheezing and asthma are independently risk factors for VOC
Sickle cell patient with dyspnea during exercise. DDx?
- Pulmonary hypertension
- Sickle cell chronic lung disease
- (Sleep disordered breathing is a co-morbidity that may be a role, but wouldn’t be top on the differential)
- Obstructive disease–asthma or wheezing (which seems to be intrinsically related to SCD)
Why is oximetry not reliable for SCD?
- increased carboxyhemoglobin in patients with sickle cell disease since faster Hb turnover. Most older oximeters in the hospital can’t differentiate between carboxy and oxygenated hemoglobin
- HbS absorbs light at a different frequency than HbA
Appearance of lamellar body in SP-B and ABCA3?
SP-B: abnormally formed lamellar body with large whorls and vacuolar inclusions
ABCA3: small and dense lamellar body, with eccentrically placed inclusions–>appearance of fried egg
BAL findings in HP?
Lymphocytosis
Decreased CD4/CD8 ratio (since there is predominance of CD8 cells)
increased NK cells
Immune pathogenesis of HP?
Sensitization to inhaled antigen–>alveolitis, with accumulation of neutrophils in the alveoli in first 48 hours–>then, increased lymphocytes and macrophages with prodominance of CD8 cells
- Both type 3 and type 4 cell mediated immune responses are involved, but there is no immune complex deposition in the lung
Patient with lupus presents with pleural effusion. Differential?
Infection is high on the differential! Patients with lupus are at high risk for pulmonary infection, even in the absence of drug side effects
- Inflammatory: pleuritis/Serositis
- Transudative due to renal failure or cardiac involvement (renal involvement would be more common)
Lupus patient who presents with fever, cough, chest pain, new infiltrate on CXR. DDx?
- Infection!!- they are at risk for opportunisitc infections like aspergillus, PJP, pseudomonas , CMV
- In general for acute pulmonary symptoms in lupus patient, think about PE, though that wouldn’t fit with fever
Other less common: - DAH, which is more likely if associated nephritis, drop in Hb or hemoptysis
- Acute pneumonitis (but this would pretty much be a diagnosis of exclusion)
Lupus patient with chronic dyspnea with exercise, chronic cough. DDx?
- chronic ILD
- pulmonary hypertension
Lupus patient with PFT showing restriction, DDx?
- chronic ILD
- Shrinking lung syndrome - I think normal DLCO corrected for VA, since there’s no parenchymal disease
- Pleural effusion
- ?DAH, but may expect increased DLCO if acute hemorrhage
What stain is used to identify hemosiderin laden macrophages?
Prussian blue stain, which will stain for iron in macrophages
What % of hemosiderin laden macrophages corresponds to diagnosis of DAH?
> 20% of 200 macrophages. There’s normal to have up to 30% of hemosiderin laden macrophages.
Describe the approach to hemoptysis
See evernote on Chapter 61
Describe the approach to diffuse alveolar hemorrhage
Evernote on chapter 61
What is the work up for hemoptysis?
What is the work up for DAH?
- CT chest with contrast (+/- sinus CT if suspecting GPA)
- Bronchoscopy - confirm pulmonary hemorrhage and get samples for infection
- Coagulation - INR, PTT, vWF, fibrinogen
- Infectious - sputum and blood culture, TB skin test
- echo to look for PH and cardiac disease
- CRP, ESR
- DAH: echo, ANA, ANCA, anti-GBM, antiphospholipid antibody, lupus anticoagulant, ESR/CRP, D dimer, anti-dsDNA
- CBC, iron studies
- Kidney: U/A, urine protein:creatinine ratio
Based on Dr. Dell:
- immune work up, including immunoglobulins
Causes of hypoxemia in a patient with sickle cell disease?
Hypoventilation:
- OSA (functional asplenia causes adenotonsillar hypertrophy and extra-medullary hematopoeisis)
- Depression of respiratory rate from use of narcotic in context of pain crisis
- Diffusion: sickle cell chronic lung disease, pulmonary hypertension
- VQ mismatch:
- Pain leading to splinting and atelectasis
- Obstructive lung disease (even in the absence of asthma)
- pulmonary thrombosis
Older patient (>2 years of age) with ILD symptoms (non-productive cough, dyspnea, poor activity tolerance)
Differential:
- Vascular: diffuse alveolar hemorrhage, cardiac: pulmonary hypertension, PVOD
- Infection - if immunocompromised–>chronic infection
- Bronchiolitis obliterans - related to post-infectious, rejection or GVHD
- aspiration
- ongoing disorder of infancy - NEHI, surfactant deficiency
- Inflammatory:
- systemic inflammatory disease - eg. lupus, scleroderma, sarcoid
- toxic exposures: pneumotoxic drugs, radiation, inhalational exposures
- autoimmune pulmonary alveolar proteinosis
- other: eosinophilic pneumonia, hypersensitivity pneumonitis, organizing pneumonia
Drugs that cause pulmonary injury? What is the timeline for lung injury?
Cytotoxic: A: ATRA, ARA-C (cytosine arabinoside) B: busulfan, bleomycin C: cyclophosphamide, carmustine IL-2 Methotrexate
Non-cytoxic:
- Antibiotics: nitrofurantoin
- IBD: mesalazine, sulfasalazine
- Seizure: keppra
- Azathioprine
*Bleomycin is the MOST important. Also remember: busulfan, cylophosphamide, carmustine
Timeline:
- typically within weeks to months of initial exposure
- with some agents such as bleomycin, carmustine (and potentially cylocphosphamide) there can be delayed toxicity:
Is there a pathognomonic type of lung injury with drug toxicity?
NO
- wide range of imaging findings: unilateral or bilateral reticular markings, ground glass opacities or consolidations.
- There can also be CT features of pulmonary veno-occlusive disease: enlarged central arteries, centrilobular ground glass opacities, septal thickening, and pleural effusion
- General findings on PFT: decreased DLCO is most sensitive, may see findings of restriction with low lung volumes
- wide of range of histologic findings: diffuse alveolar damage, hypersensitivity pneumonitis, eosinophilic pneumonia, alveolar hemorrhage, alveolar proteinosis
With alveolar proteinosis, what would you see on BAL?
- hypocellularity
- PAS positive granular material
(CHILD statement)
With pulmonary histiocytosis, what would you see on BAL?
- intracytoplasmic pentalaminar inclusion bodies, positive CD1a staining
Differential diagnosis for neutrophilia (>3%) on BAL?
- Infection –pneumonia, bronchitis, bronchiectasis
- Aspiration
- Diffuse alveolar damage/ARDS
Differential diagnosis for eosinophilia (>1%) on BAL?
- Drug reaction
- Parasitic infection
- Fungal infection - eg. PJP
- Asthma
- ABPA
- Churg Strauss
- Eosinophilic lung disease - eosinophilic pneumonia, usually >25%
Lymphocytosis (>15%) on BAL. Differential diagnosis?
- CD4+ predominant: sarcoid (often >25% lymphocytes)
- CD8+ predominant:
- Hypersensitivity pneumonitis (often >50% lymphocytes)
- Pulmonary histiocytosis
- Drug induced ILD (drug induced pneumonitis)
- Collagen vascular disease\
- Radiation induced pneumonitis
- cryptogenic organizing pneumonia
- lymphoproliferative disorder
BAL findings of Niemann pick disease?
- storage cells typical for niemann pick disease?
BAL findings for aspiration?
- Neutrophilia
- Lipid laden macrophages
neonate with severe hypoxemia respiratory failure and pulmonary hypertension. Which CHILD disorders should be tested for on genetic panel?
ACD-MPV (FoxF1), Surfactant protein B, ABCA3 and maybe surfactant protein C mutation
