Lung Disease (Miscellaneous) Flashcards

Question

Most common endoscopic finding in Down Syndrome

Answer 1

Tracheobronchomalacia

Answer 2

1) Midface hypoplasia 2) Relative macroglossia 3) Small upper airway with superficial tonsils 4) Increased secretions 5) Obesity 6) Hypotonia

Answer 3

1) Decreased pulmonary reserve due to morphological differences 2) Poor immune function 3) GERD 4) Aspiration 5) CHD 6) Thoracic cage malformations

Answer 4

1) Immunization 2) Immune: immunoglobulin levels, functional antibodies, lymphocyte subsets 3) Yearly flu shot 4) Pneumococcal vaccine after 2yrs 5) Consider prophylactic antibiotics with frequent infections

Answer 5

Pulmonary venous HTN Decreased lymphatic flow Left to Right shunts

Answer 6

1) Birds (most common in children) 2) Farmer's lung 3) Drugs 4) Bagassosis 5) Humidifiers

Answer 7

``` BAL = lymphocytosis (increased CD8) and increased NK cells Bx = alveolitis, non-caseating granulomas, giant cells, foamy alveolar macrophages/fibrosis ```

Answer 8

1) Symptoms compatible with hypersensitivity pneumonitis 2) Evidence of antigen exposure 3) Radiographic changes consistent with hypersensitivity pneumonitis 4) BAL lymphocytosis (CD8) 5) Lung biopsy with consistent histology 6) Positive natural challenge

Answer 9

CXR: reticulonodular infiltrates, linear opacities HRCT: Acute: GGO Subacute: Micronodules, Air-trapping Chronic: fibrosis +/- honeycombing, emphysema

Answer 10

1) Bibasilar rales 2) Decreased DLCO 3) Hypoxemia 4) Clinical presentation

Answer 11

Restriction with decreased volumes, low DLCO

Answer 12

1) Interstitial lymphocytic-histiocytic cell infiltrate 2) Bronchiolitis obliterans 3) Non-necrotizing granulomas

Answer 13

1) Stop antigen exposure 2) Steroids 3) Supportive

Answer 14

- ILD - Pulmonary HTN - Aspiration - Cardiomyopathy - Bronchiectasis - Hemorrhage PFT = restriction and low DLCO

Answer 15

- Alveolar epithelial cell type 2 hyperplasia - Interstitial thickening with mesenchymal cells - Fibrosis (later disease) - Proteinaceous material and foamy macrophages

Answer 16

NKX2-1: Alveolar simplification SP-B: Poorly organized lamellar bodies ABCA3: Absent or small, abnormally formed lamellar bodies with fried egg appearance

Answer 17

80% phospholipids 8% protein 8% lipids (cholesterol)

Answer 18

1) Cumulative dose 2) Patient age 3) Prior/concurrent radiation 4) Oxygen therapy 5) Other toxic drugs

Answer 19

1) History of ingestion of drug known to cause injury 2) Clinical manifestations caused by drug 3) Other causes ruled out 4) Improvement after drug discontinuation 5) Exacerbation with resuming drug

Answer 20

Macrophages 80-90% Lymphocytes 5-10% Neutrophils 1-2% Eosinophils 0-1%

Answer 21

4mg/kg 2% = 20mg/ml 1% = 10mg/ml

Answer 22

Constrictive: peribronchial fibrosis Proliferative: airway obstruction by intraluminal polyps of inflammatory granulation tissue, masson bodies

Answer 23

Excessive proliferation of granulation tissue -> consists of loose collagen-embedded fibroblasts and myofibroblasts involving alveolar ducts + alveoli +/- bronchiolar intraluminal polyps

Answer 24

Steroids (IV or PO) | Macrolides

Answer 25

1) Lymphocytosis (increased CD4:CD8 ratio) 2) no eosinophils, stain S-100, CD1a, langerin 3) Acute = neutrophilia, >48hrs = lymphocytosis, increased CD8 4) Gross blood, increasing with each sample 5) Lipid laden macrophages

Answer 26

Foamy alveolar macrophages | Type 2 alveolar cell hyperplasia

Answer 27

Acute: - children - Smoking = risk - Male predominance - no underlying asthma risk - presents as acute febrile illness - BAL > 45% eos - normal blood eosinophils - some elevation in IgE - responds to steroids - No role for Xolair

Answer 28

Ground glass opacity with superimposed interlobular and intralobular septal thickening

Answer 29

ARDS, bacterial pneumonia, PAP, DAH, sarcoidosis, vasculitis, pulmonary edema, chronic eosinophilic pneumonia, lipoid pneumonia, COP, PJP

Answer 30

Mets Infectious granuloma (TB, fungal, atypical mycobacteria), Infections (abscess, echinococcus, PJP, aspiration) Benign (hamartoma, lipoma, fibroma) Vascular (AVM, infarct) Bronchogenic cyst Inflammatory (GPA, rheumatoid inflammation, sarcoid)

Answer 31

Inflammatory (GPA, Sarcoid) Infection (TB, fungal, septic emboli) Thrombotic Mets/Malignancy

Answer 32

Mass Aspiration Hemorrhage Atelectasis

Answer 33

Diffuse consolidative with interstitial pattern

Answer 34

``` Air Pus Blood FLuid Protein ```

Answer 35

``` Age (esp 2-4 yrs) Pulmonary infection (mycoplasma) Fat embolism Post-op atelectasis Low concentration of fetal hemoglobin Bronchospasm due to asthma Higher WBC count Genetics (HbSS) ```

Answer 36

Recurrent ACS

Answer 37

ACS (second most common cause of hospitalization)

Answer 38

Chronic = 4-8 weeks Dry: Allergic rhinitis, asthma, GERD, TB malacia, habit cough, ILD, post infectious cough (pertussis, mycoplasma), drugs (ACEi) Wet: CF, PCD, retained FB, Aspiration, immunodeficiency, chronic endobronchial suppurative disease (non CF bronchiectasis, PBB) Other: chronic infection (TB, chlamydia, CMV), non-infective bronchitis, mediastinal mass

Answer 39

1) Immune reconstitution inflammatory syndrome (develops in context of recovery of CD4 cells following initiation of ART) 2) ILD (lymphocytic infiltrate in the peribronchial and pervascular tissue and interlobular space) 3) Pulmonary HTN 4) Recurrent Infections 5) Bronchiectasis and BO 6) Malignancy

Answer 40

Low CD4 count prior to initiation of ART | Opportunistic infection treatment proximal in time to ART initiation

Answer 41

Acute = Interstitial mononuclear cell infiltrates, Granulomas and foamy macrophages Subacute = (classic triad) Interstitial lymphocytic-histolytic cell infiltrates, BO, scattered poorly formed non-necrotizing granulomas Chronic = giant cells, granulomas, NSIP, UIP pattern

Answer 42

``` Upper = chronic sinusitis , nasal septal perforation/ulcer, oral ulcers, subglottic stenosis Lower = tracheal or bronchial stenosis, diffuse alveolar hemorrhage , granulomas (nodules) Antibodies = PR3 and MPO ANCA, mostly PR3 which is more specific. ```

Answer 43

Type I – Inflammatory casts – contain fibrin and eosinophilic infiltrate , e.g.,CF, asthma Type II – noninflammatory casts – acellular containing mucin and fibrin without inflammatory infiltrated e.g., plastic bronchitis in post-Fontan patient

Answer 44

PAS stains for polysaccharide, glycoprotein, glycolipids), so this makes sense why PAS positive in fungal Dx: Pulmonary Alveolar Proteinosis Diff: Fungal infection (PAS positive) ILD (Pulmonary fibrosis, sarcoidosis can be PAS positive)Surfactant protein deficiency (proteinaceous secretions) Surfactant protein deficiency (proteinaceous secretions) Periodic acid–Schiff (PAS) is a staining method used to detect polysaccharides such as glycogen, and mucosubstances such as glycoproteins, glycolipids and mucins in tissues.

Answer 45

Microscopic findings: - No specific diagnostic features of disease, with an absence of extensive inflammation, reactive injury, architectural distortion, and fibrosis seen on lung biopsy - Minor and nonspecific changes involving the distal airways including: - Mildly increased airway smooth muscle - Mildly increased numbers of alveolar macrophages - Increased number of ‘ clear cells’ within bronchioles - Patchy mild peri airway lymphocytic inflammation and fibrosis commonly seen Immunohistochemical Features: - Consistent increase in Bombesin-immunoreactive cells within bronchioles - > 75% of non cartilaginous airways contain immunopositive cells, present in small clusters (need 8-10 airways to evaluate) - One or more bronchioles with > 10% of airway epithelial cells immunopositive - Frequently increased size and number of neuroepithelial bodies around alveolar ducts.

Answer 46

Cilia Ultrastructure – Classic 9+2 Arrangement Commonest defect = Outer dynein arm defect Diseases due to sensory ciliopathy= PCKD, Bardet-Biedl Syndrome, Alstrom Syndrome, Joubert, Retinitis pigmentosa

Answer 47

Enlarged internal bronchial diameter Signet ring sign (bronchi : vessel ratio >1.0) Failure of airway to taper in lung periphery Bronchial wall thickening ( Tram track) Mucus plugging / impaction ( Tree in bud pattern) Mosaic perfusion Air trapping on expiration Air-fluid levels in distended bronchi

Answer 48

Type of obstructive lung disease of the small airways. It is a rare disease with characteristic features of fibrosis of terminal and distal bronchioles and spirometry showing airflow obstruction.

Answer 49

1. Infection/other insult 2. Injury/destruction of airway epithelium 3. Acute and chronic inflammation leading to: - Repair to healing OR repair by proliferation of granulation tissue 4. Fibrosis of airway wall and lumen 5. Obliteration of airway lumen **Subepithelial inflammation and fibrotic narrowing of bronchioles leading to in/complete obstruction 2 phases: inflammatory and fibrotic

Answer 50

Post Infectious - Adenovirus (1,3,7,21) - Measles, RSV, mycoplasma, influenza, parainfluenza

Answer 51

Post-transplant (chronic rejection, GVHD) Connective tissue disease (RA, Sjogrens, SLE) Toxic fume inhalation (NO2, NH3) Chronic hypersensitivity pneumonitis (avian, mold) Aspiration (GERD, foreign body) Drugs (Pencillamine, Cocaine) SJS (idiopathic, drug-induced, infection related)

Answer 52

most common = physiologic features of respiratory obstruction - Progressive dyspnea, non-productive cough - weeks-months. - O/E: Wheeze, crackle possible - Children - “incomplete” recovery from respiratory illness, symptoms persist >60days.

Answer 53

Abnormality = Irreversible airway obstruction - Spiro: N/↓ FVC, ↓FEV1, ↓V1/VC, ↓FEF25-75. No BD response. - Pleth: Air-trapping, incr RV/TLC. Nrml TLC. - Subset show restrictive or mixed disease. - DLCO may be ↓ in severe or progressing dz.

Answer 54

Often normal. | Hyperinflation & incr linear/reticular/interstitial markings suggestive.

Answer 55

High-Res CT - Inspiratory/Expiratory w/o contrast = definitive non-invasive test. 1. Mosaic attenuation / perfusion = patchy areas of decreased lung density w/ reduced vascular caliber → due to bronchial air trapping 2. Air-trapping - esp. on expiratory view 3. Advanced disease: central bronchiectasis (large airways = dilated, thickened) 4. Paucity of ground glass lesions.

Answer 56

Incr WBC - Incr. PMNs, Incr. Lymps acutely. Late: T-cell drive → Incr CD40

Answer 57

Biopsy - Complicated by patchy disease - Often not done, at patient ill. Yield not ideal. Clinically: Based on story, imaging - may be reasonable. HRCT important.

Answer 58

- Natural history - highly variable - Pediatric - Post-Infectious = Low mortality, high chronicity. Some improve gradually with time. - Azithromycin - most effective - anti-inflammatory - Difficult to Rx: little response to glucocorticoid, little consistent response to others - Lung transplant for severe disease Swyer-James develops in ⅓ = Unilateral hyperlucent lung, ↓ vascularity, air trapping = smaller, darker lung on chest radiograph - CT shows actually bilateral disease: diffuse, asym, pathcy lobar air trapping - Post-infectious, fibrotic healing of immature lung Generally non-progressive if exposure ceases / cause resolved Increased risk of mortality from respiratory disease Transplant related BO generally progressive

Answer 59

- Supportive care: Oxygen, Nutrition, Antibiotics if infected, GERD management, flu vaccination Acute Management: - Pulse steroid: 30mg/kg max 1-gram, once daily x 3 days, then monthly 3-day treatments if initial is beneficial - no evidence of benefit - IVIG, TNF-alpha has been used - little evidence - Azithromycin chronic 3x/weekly - anti-inflammatory: decr PMNs, decr cytokines - ICS, LTRAs have been trialed too

Answer 60

- Hosp >30 days - Multifocal pneumonia - Hypoxia - Hypercarbia - Need for PICU - Need for Mechanical Ventilation - Corticosteroid or b2-agonist need during the acute illness

Answer 61

BO = primary non-infectious pulmonary complication of allogenic HSCT - Typically w/n 2-years post-transplant, but may occur several years post - Incidence ~5% post HSCT - More common with acute GVHD - query form of chronic GVHD - Assoc w/ Older age of donor/recipient, worse HLA match, GERD, aspiration, busulfan conditioning, low gamma-globulin levels, smokers. - RSV, Paraflu w/n 100 days post transplant incr risk - Solid lung transplant: 10-year risk of disease ~70%. Tacrolimus = Less BO as compared to cyclosporine Rx = Increase in immunosuppresive agents, adjuvant Rx (macrolides, LTRA, ICS) - The literature remains poor. - Azithromycin response in ~50% (PFT improvement).

Answer 62

Formally known as BOOP (bronchiolitis obliterans with organizing pneumonia) Histologically distinguished by patchy areas of consolidation with polypoid plugs of loose organizing connective tissue in the respiratory bronchioles and alveolar ducts Proliferative bronchiolitis is manifest by patchy infiltrates on CXR and by restriction on PFT Often improves with steroids (unlike other post HSCT complications) and macrocodes as adjunctive tx

Answer 63

Subacute = < 3 mos Non-specific symptoms - cough/dyspnea Often mild hypoxemia Requires exclusion of common causes of diffuse lung disease

Answer 64

Bronch indicated in all suspected COP - rule out infections, consider malignancy Mixed cell differential - lymphs 20-40%, CD4/CD8 ratio decreased, neuts 10%, Eos 5%

Answer 65

CF | Worldwide non-CF bronchiectasis more common

Answer 66

Pathologic state of the conducting airways manifested by radiographic evidence of bronchial dilation and clinically by chronic productive or wet cough.

Answer 67

Clinical syndrome where symptoms of chronic endobronchial suppuration exist with or without c-HRCT evidence of bronchiectasis. Presentation: symptoms are identical to bronchiectasis, including a prolonged moist or productive cough responsive to antibiotics, hemoptysis, exertional dyspnea, increased airway reactivity, growth failure, and recurrent chest infections.

Answer 68

Timing of scan is important - should be done during NON-ACUTE STATE At least 2 CT scans required to meet definition of “irreversible bronchiectasis”

Answer 69

1) Impaired immune function - SCID, CVID, AT, HIV etc 2) Ciliary dyskinesia (Primary, functional) 3) Abnormal mucus (CF) 4) Clinical syndromes - Young's syndrome, Yellow nail lymphedema syndrome, Marfan syndrome, Usher syndrome 5) Congenital tracheobronchomegtly - Mounier-Kuhn syndrome, Williams-Campbell, Ehlers-Danlos 6) Aspiration syndromes - Recurrent small volume, primary aspiration, TEF, GERD 7) Obstructive bronchiectasis (FB, tumour, LN) 8) Other pulmonary disease association - ILD, BO, ABPA, BPD, Tracheobronchomalacia 9) Others - Alpha-1 antitrypsin deficiency, post transplant, autoimmune, posttoxic fumes, eosinophilic lung disease

Answer 70

1) Structural airway abnormalities, such as bronchomalacia, endobronchial tuberculosis, - central airway compression, or retained aspirated foreign bodies → impair mucous and bacterial clearance. 2) Persistent airway injury and narrowing associated with bronchiolitis obliterans (due to viral injury or following lung transplantation) 3) Recurrent airway injury, such as aspiration syndromes Additional factors: inhaled irritants/pollutants, impaired upper a/w defenses (sinus disease & eustachian tubes = sanctuary sites for bacteria, variations in host inflammatory response. Other important etiologies - Acute Lower Respiratory Infections (including pneumonia) - AKA Post-infectious - Upper airway infection and aspiration - Public Health Issues - Genetics

Answer 71

Neutrophilic inflammation (TNF-A, IL-8, IL-6) Intraluminal secretion accumulation Distal airway obliteration

Answer 72

Cylindrical Varicose Cystic (aka saccular)

Answer 73

Rule of 3rds (w/ Rx): 1⁄3 improve, 1⁄3 stable but symptomatic, 1⁄3 worsen

Answer 74

Only significant predictor of FEV1 decline (1 study) = freq of exacerbations requiring hosp

Answer 75

Local progression (ie 𝚫 to saccular) > extension to new areas, (both can occur)

Answer 76

+ve asthma Bilateral involvement Saccular bronchiectasis

Answer 77

Chronic Wet Sounding Cough

Answer 78

Persistent/recurrent wet or productive cough of purulent or mucopurulent sputum Others: ○ Hyperinflation / chest wall deformity (5-60%) ○ Clubbing (5-60%) - may disappear post Rx. ○ Exertional dyspnea ○ Recurrent wheeze/chest infection ○ Hemoptysis - less common in children, may be presenting symptom (late) ○ Auscultation range from normal → coarse inspiratory crackles ○ Reduced oxygen saturations (late) ○ Pulmonary hypertension with associated cardiac findings (late)

Answer 79

``` Bronchiolitis obliterans Asthma GERD Hypertorphic osteoarthropathy Cardiac dysfxn +/-Pulmonary hypertension (late) ```

Answer 80

1. Confirm diagnosis 2. Define distribution and severity of airway involvement 3. Characterize extrapulmonary involvement (AKA cor-pulmonale) 4. Identify treatable and familial causes of bronchiectasis

Answer 81

1. Signet ring sign 2. Enlarged internal bronchial diameter 3. Failure of airway to taper normally while progressing to lung periphery 4. Presence of peripheral airways at CT periphery 5. Presence of associated abnormalities - bronchial wall thickening - mucoid plugging or impaction 6. Mosaic perfusion 7. Air trapping on expiration

Answer 82

False Positives - Physiologic constriction of pulmonary artery - Artifacts from cardiac pulsation and respiratory motion - Pseudobronchiectasis or transient bronchial atresia - Increased bronchoarterial ratio in patients considered normal, asthmatics or high altitude False Negatives - Inappropriate HRCT protocol - Poor image due to movement artifacts - Nonuse of high resolution techniques

Answer 83

1) Severity of bronchiectasis 2) Presence of peribronchial thickening 3) Extent of bronchiectasis (# BP segments)

Answer 84

``` Baseline immune function CBC HIV status Sweat test and genotype Radiology (CXR, HRCT) Aspergillosis serology Cilial biopsy Sputum ``` ``` Additional: Bronchoscopy GERD investigations Barium swallow (TEF, esophageal abnormalities) Mantoux test Further immune tests Video fluoroscopy ```

Answer 85

Indicated to identify obstructive bronchiectasis: Intraluminal (FB, tumor) Mural (bronchomalacia) Extramural 5 types of classification (5 = no abnormality, most common = type 1: mucosal abnormality/inflammation only)

Answer 86

No - especially for localized disease (diffuse - FEV1 reflects disease severity not activity) Other PFT abnormalities: - high RV - Lower aerobic capacity - lower maximal ventilation at max exercise

Answer 87

S. pneumo, non-typable H Flu, moraxella

Answer 88

Frequency of hospital exacebation

Answer 89

Pulmozyme = contraindicated Hypertonic saline = increases airway clearance, improves lung function and decreases exacerbation Insufficient evidence to recommend macrolides routinely as anti-inflammatory Chest physiology lacking in evidence

Answer 90

Poor control of symptoms (purulent sputum, frequent exacerbations) despite optimal medical therapy Poor growth in spite of optimal medical therapy Severe and recurrent hemoptysis uncontrolled by bronchial artery embolization (relative) localized disease with moderate persistent symptoms

Answer 91

Widespread bronchiectasis Young child Minimally symptomatic disease

Answer 92

Neutrophilic | high IL-6, IL-8, TNF-alpha

Answer 93

Qf = Kf[(Pc − Pis) − σ(πpl − πis)]

Answer 94

1) Basement membranes of capillary endothelium and alveolar epithelium fused in some areas 2) Secreted matrix/structural proteins bw endothelial +epithelial basement membrane provides channel for water and protein to travel to lymphatics for absorption 3) Pulmonary capillaries have a continuous endothelium w tight intercellular junctions 4) Alveolar epithelial membrane has tighter cellular junctions 5) Polyhedral shaped alveoli

Answer 95

1. Interstitial spaces of alveolar capillary septae - accommodates few hundred mL (faster resolution) 2. Alveolar space - accommodates 30mL/kg body weight

Answer 96

They are distributed throughout lung’s interstitium + are stimulated by the presence of edema (increased RR)

Answer 97

1) Pulmonary capillary pressure = LA –PA pressure +40% 2) Interstitial Forces 3) Microvascular filtration coefficient and vascular permeability 4) Lymphatic clearance

Answer 98

A measure of a membrane's permeability to water Specifically, the volume of fluid filtered in unit time through a unit area of membrane per unit pressure difference

Answer 99

Vascular permeability/reflection coefficient . Endothelial membrane has pores. Fluid filtering through a pore will drag some protein with it. The larger the protein relative to the size of the pore, the less protein will be dragged. When the protein is the same size or larger than the large, the relection coefficient is 1. As the size of the protein becomes smaller, σ approaches zero.

Answer 100

- Increased capillary hydrostatic pressure (most common) - Decreased capillary oncotic pressure - Decreased interstitial hydrostatic pressure - Increased pulmonary vascular surface area - Increased vascular permeability in fluid-exchanging vessels

Answer 101

1) Lymphatics (most important) 2) Venular end of the microvascular bed (where Pmv has decreased and the balance of Starling forces can favor reabsorption) Alveolar edema fluid, after being actively transported across the epithelium, is returned to the circulation either by direct entry into the microvasculature across the thin side of alveolar capillary membrane or by the lymphatics after it has been translocated back to the interstitial space.

Answer 102

1) Normal alveolar walls and no excess fluid in perivascular connective tissue spaces. 2) Initial fluid leak. Fluid flows to the interstitial space (at subatmospheric pressure) around the conducting vessels and airways. 3) Tissue space fills, alveolar edema increases, and fluid begins to overflow into the alveoli, notably at the corners where curvature is pronounced. 4) Quantal filling. Individual alveoli reach a critical configuration at which existing inflation pressure can no longer maintain stability. Distal lung units in different regions of the lung will be at different stages of fluid accumulation because of their regional differences in pressure, alveolar- capillary membrane integrity, and gravitationally dependent factors.

Answer 103

The presence of edema increases airway resistance. As the airways narrow, closing volume increases and alveolar gas exchange is impaired because of the resultant low V/Q ratio. At this stage, hypocapnia results from the J receptor vagally mediated reflex hyperventilation independent of the presence of hypoxemia. As edema worsens and alveolar flooding occurs, there is further hypoxemia as the blood shunts past nonventilating alveoli. Respiratory acidosis may supervene if the patient is depressed by sedation or if exhaustion develops.

Answer 104

- tachypnea (stimulation of J receptors) - crackles (fluid in terminal airways) - rhonchi + wheezes (when fluid moves up to larger airways) - retractions (generate more negative pleural pressures to overcome decreased compliance) - grunting (create PEEP to prevent collapse of distal lung units)

Answer 105

Initially, vascular engorgement can lead to increase in DLCO by increasing the amount of perfused vasculature --- eventually reduced DLCO With alveolar flooding, there is air trapping, increased vascular resistance, decreased lung volumes, decreased dynamic compliance, and progressive hypoxemia

Answer 106

CXR - Kerley (septal) lines: interlobular sheets of abnormally thickened or widened connective tissue - Peribronchial cuffing - Alveolar filling defect with air bronchograms in severe forms - Obstruction hyperinflation CT - Regional edema and microatelectasis = heterogenous and shift with the position of the patient (densities often appear in gravitationally dependent lung regions)

Answer 107

1) High pressure pulmonary edema (L sided heart disease, obstructive lesions, heart failure, increased pulmonary blood flow etc) 2) Airway obstruction (diffuse small airway obstruction results in a lag in the expansion of the lung in spite of development of very negative intrathoracic pressure) 3) Re-expansion pulmonary edema 4) Neonatal RDS 5) Neurogenic pulmonary edema 6) Acute lung injury and ARDS 7) High Altitude pulmonary edema 8) Inhalation of toxic agents

Answer 108

1) Reverse hypoxemia: O2, Positive pressure 2) Reduce the rate of fluid filtration (treat the disorder) 3) Minimize treatment related lung damage 4) Augment rate of clearance of airspace fluid

Answer 109

In adults: when extravascular lung water (EVLW) is increased by approximately 35%

Answer 110

high pressure (ie. CHF) vs high permeability pulmonary edema (ie. ARDS) - most pts with pulmonary edema have both increased permeability and elevated pulmonary artery pressures - no tests available to reliably distinguish bw 2 causes

Answer 111

Consequence of inflammatory process at alveolar-capillary interface Increased alveolar capillary permeability à flooding of alveoli with protein rich fluid, leading to: - Impaired gas exchange - Impaired surfactant function

Answer 112

Onset: Acute (within 7 days of an “event”) CXR: Bilateral opacities Not fully explained by cardiac failure or fluid overload Severity: · Mild: PaO2:FiO2 = 200-300 · Moderate: PaO2:FiO2 = 100-200 · Severe: PaO2:FiO2 = < 100

Answer 113

1. Triggered by direct or indirect injury 2. Acute exudative phase with pulmonary edema, cytokine release, activated neutrophils 3. Fibroproliferative phase (may lead to fibrosing alveolitis) 4. Recovery Stage

Answer 114

Pulmonary edema, cytokine release, activated neutrophils Intrapulmonary shunting, reduced FRC, decreased compliance CXR: diffuse bilateral homogenous parenchymal disease CT: may see heterogeneity (severe damage to some lung, and less damage elsewhere)

Answer 115

1) Fully aerated normal (typically non dependent) (AKA “Baby lung”) 2) Poorly aerated (injured by recruitable) 3) Non-aerated consolidated/atelectatic lung

Answer 116

May lead to fibrosing alveolitis Increased alveolar dead space, hypoxia, reduced lung compliance If patients progress to this stage, outcomes are worse

Answer 117

Occurs within 10-14 days Gradual improvement in lung compliance and oxygenation Mechanism not well understood Norm is for patients without underlying chronic lung disease to return to normal lung function

Answer 118

Direct (pulmonary) causes

Answer 119

Characterized by a primary injury to the alveolar epithelium | Results in intra-alveolar edema, reduced lung compliance, with preservation of chest wall compliance

Answer 120

Primary insult is systemic, with the major injury occurring to the capillary endothelium Results in interstitial edema, with greater reduction of compliance in the chest wall

Answer 121

Predominantly consolidation Differences in mechanism of injury and pathology may explain why pulmonary causes tend to have more refractory hypoxemia, with resistance to recruitment maneuvers and prone posturing, but respond better to surfactant

Answer 122

Predominantly atelectasis

Answer 123

Blood gas Oxygenation Index (OI = (MAPxFiO2)/ PaO2) Ventilation Index [VI = (PaCO2 x PIP x RR)/1000)] Lung injury score: Incorporates CXR, PaO2/FiO2, PEEP and compliance - rarely used

Answer 124

Surfactant Protein B, IL-6, Coagulation factor V (F5)

Answer 125

1) Mechanical properties of lungs of children and infants differ from adults (Chest wall compliance is inversely related to age) 2) Infants have low inherent elastic recoil 3) Lung volume to body weight is greatest at 2 years 4) Mortality for children is less than adults 5) High FiO2 is associated with worse outcome in children, but not adults

Answer 126

Barotrauma : physical disruption of alveoli Volutrauma: over-distention of alveoli Atelectrauma: Recruitment and derecruitment of collapsed alveoli Biotrauma: activation of inflammatory process Oxygen toxicity

Answer 127

High PIP, large Vt, Low PEEP, and +/- high FiO2 (High PEEP is protective)

Answer 128

Vt< 10ml/Kg PIP < 30cmH20 Higher PEEP (5-20cmH2O)

Answer 129

Non-invasive High Frequency Oscillatory Ventilation (HFO) Airway Pressure Release Ventilation (APRV) Neuronally Adjusted Ventilatory Assist (NAVA)

Answer 130

``` Prone Posturing Inhaled Nitric Oxide (iNO) Surfactant Corticosteroids (controversial) Neuromuscular blocking agents (NMBA) Beta Adrenergics ECLS Tracheostomy ```

Answer 131

Increased edema in ARDS is due to increased permeability and (to a lesser extent) increased capillary hydrostatic pressure B agonists may reduce edema by: - Upregulation of Na transport - Pulmonary vasodilation and reduction of pulmonary vascular pressure (reduces capillary hydrostatic pressure) - May independently decrease endothelial permeability - In adults: lessened the lung water content and lessened the inspiratory airway pressures - In children: may be associated with reduced mortality (no RTC)

Answer 132

Process resulting in primary respiratory impairment from submersion/immersion in liquid’ – now encompasses fatal and non-fatal immersion

Answer 133

Aspiration Infection Lung injury

Answer 134

Salt water: osmotic gradient – shift fluid into alveoli; does not result in significant hemodynamic compromise from fluid shifts in animals (more then freshwater) Freshwater rapidly absorbed into systemic circulation and maybe edema secondary to neurogenic causes, forced inspiration against closed glottis and altered surfactant or pulmonary capillary permeability

Answer 135

i. respiratory symptoms (coughing/rapid breathing/exercise intolerance) ii. physical signs (crackles/adventitious breath sounds/clubbing/retractions etc) iii. hypoxemia iv. diffuse parenchymal abnormalities on imaging AND must r/o more common causes of diffuse lung disease (CF, PCD, immunodeficiency, aspiration etc) Children < 2 y.o.a with chILD tend to have diagnosis in category ‘more common in infancy’ and those > 2 y.o.a tend to have diagnosis in category ‘d/o related to systemic disease’ and ‘immunocompromised host’

Answer 136

1. Developmental D/O (ACD-MPV) 2. Growth abnormality d/o (Pulmonary hypoplasia, CLD (neo or cardiac)) 3. Specific conditions of unknown etiology (NEHI, PIG) 4. Surfactant dysfunction (Surfactant protein B or C def, ABCA def, NKX2.1 mutation)

Answer 137

Collagen vascular disease Storage disease Sarcoidosis LCH

Answer 138

Infection/post-infection Hypersensitivity pneumonitis Aspiration Eosinophilic pneumonia

Answer 139

Opportunistic infection Transplantation and rejection Therapeutic intervention (ie. chemotherapy)

Answer 140

Pulm HTN Cardiac dysfunction VOD Lymphatic d/o

Answer 141

1. Full Hx; O/E 2. Specific investigations to r/o CF, PCD, aspiration, immunodeficiency, HP and autoimmune disease 3. Imaging: CT better for NEHI, BO, HP, PAP 4. Echo to assess for masqueraders 5. Infant PFT’s if available (reliable in NEHI – a/w obstruction and gas trapping) 6. Genetic testing 7. Bronch/BAL: r/o anatomic abnormalities, PAS staining r/o infection 8. Biopsy – if test results unclear; no other way to diagnose pulmonary hemorrhage with capillaritis, PIG, alveolar simplification, ACD/MPV, NEHI, HP, follicular bronchiolitis etc

Answer 142

Mixture of lipid/proteins --> reduces ST at air-liquid interface and thus prevents alveolar collapse – critical function maintained by maintaining balance between production and clearance complex mix of phospholipids/neutral lipids/specific proteins made by type II alveolar epithelial cell (AEC2) stored in lamellar bodies and secreted by exocytosis into alveolar lumen

Answer 143

RDS RDS is due to surfactant deficiency from prematurity, however, number of d/o associated with single gene defects causing abnormal surfactant production or clearance (homeostasis)

Answer 144

major lipid: phosphatidylcholine (PC), large fraction of which contains two palmitic acid side chains that are fully saturated (dipalmitoyl or disaturated phosphatidylcholine – DPPC or DSPC) and its presence is critical for surfactant function

Answer 145

member of ATP-binding cassette family of membrane transporters Located on limiting membrane of lamellar bodies and important for transport of phospholipids into lamellar bodies during surfactant synthesis

Answer 146

Lowering surface tension- two extremely hydrophobic surfactant proteins which reduce ST in vitro and in-vivo surfactant deficiency in animals and both are present in the surfactant used for RDS

Answer 147

important in local host defence because they can bind to variety of micro-organisms

Answer 148

(also called thyroid transcription factor) | A transcription factor that binds to promoter regions of DNA important for proper expression of the surfactant proteins

Answer 149

Surfactant is recycled into AEC2s and catabolized by alveolar macrophages Catabolism dependent on macrophage maturation which depends on GM-CSF binding receptor at cell surface to initiate signaling events which regulates multiple alveolar macrophage functions including the ability to catabolize surfactant components

Answer 150

- hydrophobic protein that reduces ST and plays role in regulation of other surf proteins - encoded by single gene (SFTPB on Chrom 2) - produced by AEC2’s - AR inheritance (loss of fxn mut – most often is frame-shift with Premature stop codon) - increased in northern Europeans - complete deficiency – results in lethal phenotype with clinical features similar to RDS that is only treatable with lung Tx - partial SP-B deficiency – intermediate survival - SPB has role in SPC processing, therefore SPB deficiency can cause increase in abnormal SPC and an SPC deficiency

Answer 151

i. interstitial fibrosis/AEC2 hyperplasia (seen in number of other d/o of surf production) ii. alveolar proteinosis can be seen iii. poorly organized lamellar bodies, with vacuolar inclusions CXR would look like RDS - genetic testing and protein expression testing for SP deficiency

Answer 152

Lung transplant

Answer 153

- extremely hydrophobic peptide - Single Gene, on Chrom 8 - SP-C, like SP-B, enhances ST lowering ppties of surfactant lipids and is present in mammalian derived surfactant preps used to treat RDS in neonates - AD inheritance - genetic modifiers seem to be important in the development of SP-C related lung disease - de Novo mutations occur - spectrum of disease – can be seen in the same family in an infant in one generation and in previous generations as adult ILD; also genes not on the SFTPC gene may also result in SP-C deficiency - disease mechanisms: i. may be from lack of functional SP-C OR ii. from toxic accumulation of abnormal proSP-C (may be directly toxic to AEC2’s) “Gain of toxic function”, ie the protein is misfolded and causes secondary damage Clinical features in children/adults: chronic respiratory symptoms (dyspnea/cough) and signs (tachypnea, crackles), FTT, clubbing, hypoxemia and supplemental oxygen Variable age of onset – some have distress after birth, others asymptomatic until adulthood - some children requiring mechanical vent may improve over time

Answer 154

- CXR/CT: ground glass opacities, peripheral cysts - SP-C in BAL may be absent - genetic testing and protein expression testing for SP deficiency - Pathological findings: i. can be non-specific – NSIP or chronic pneumonitis of infancy or DIP

Answer 155

- no specific Tx exists - people have tried: i. steroids ii. hydroxychloroquine iii. azithromycin - none of these have proven efficacy

Answer 156

- member of ATP binding cassette family of transmembrane proteins - hydrolyze ATP to transport substances across membranes – particularly important to transport DSPC/DPPC - encoded by single gene (ABCA3 on Chrom 16) - expression – developmentally regulated with increased expression late in gestation and increased by glucocorticoids - mostly expressed in AEC2’s – localize to limiting membrane of lamellar bodies - Also expressed in kidney, gut, thyroid, brain - AR inheritance (loss of function mutation) Present similar to SP-B deficiency – as patient with RDS and severe surfactant deficiency in term/near term infant; however, there is a milder form presenting later similar to children with SP- C deficiency, maybe due to some retained ABCA3 fuxn - > 100 mutations described - most frequent cause of surfactant deficiency

Answer 157

- BAL - markedly reduced DPPC content - ultrastructural findings: - absent/abnormal lamellar bodies - small/dense inclusions eccentrically placed in abnormal lamellar bodies gives ‘fried egg’ appearance - distinct from ultrastructural appearance in SP-B def where lamellar bodies are larger and loosely packed (these findings are in severe ABCA3 def)

Answer 158

no proven efficacious therapy - steroids increase ABCA3 transcription in vitro, thus rationale for use of steroids to augment any remaining fuxn but not proven to help - hydroxychloroquine and azithro have been used with little data to speak to efficacy - lung Tx may be necessary with similar survival for age-matched controls

Answer 159

- NKX2.1 – also called thyroid transcription factor (TTF1), is a TF important for development of thyroid gland, CNS (basal ganglia) and in lung - critical for expression of SPA, B, C & ABCA3 - On Chrom 14 - loss of one allele (haploinsufficiency) could result in lung disease - mutation/deletion in NKX2.1 may result in neurologic symptoms (hypotonia/chorea), hypothyroidism and/or lung disease (not necessarily all three, but any combo) - NKX2.1 important for expression of SP-A, B and C and ABCA3 - Unclear if it is the NXK2.1 or the resultant reduced expression of SPA,B,C or ABCA3 that causes lung disease - mutations result in phenotype of RDS (surf def) and ILD (surf dysfunction) - pulmonary infection because reduced SP-A - variable spectrum of disease

Answer 160

Pathology | - Similar to those of other surfactant dysfunction - Alveolar simplification

Answer 161

Referring to PAP Heterogenous group of diseases defined histopathologically by finely granular, lipoproteinaceous material filling pulmonary alveoli and terminal airspaces This material stains with eosin stain and periodic acid Schiff stain (PAS stain), has identical features to surfactant and frequently contains cholesterol needles May also see alveolar distortion/fibrosis depending on underlying pathology variable histologic features result from variable diseases that can cause this picture

Answer 162

Autoimmune PAP – caused by autoantibodies to GM-CSF (granulocyte macrophage colony stimulating factor) which is very important in signaling for alveolar macrophages to catabolize surfactant – thus if have autoAb’s you hamper this signaling and get surfactant build-up PAP; Hereditary forms of PAP – caused by abnormal GM-CSF receptor which are also referred to as primary PAP (CSF2RA, CSF2RB)

Answer 163

Occurring in association with an underlying disease such as: ▪ Hematologic d/o (MDS, malignancy, aplastic anemia) ▪ Chronic infection (HIV) ▪ Toxic inhalation (silica, metal dust) ▪ Genetic disease (LPI) ▪ SCID

Answer 164

- 90% of all PAP - caused by immune attack (autoAb) to GM-CSF that blocks signaling to alveolar macrophages neutralizing the ability to catabolize surfactant - prevents terminal differentiation of alveolar macrophages - impaired ability for defense and surf catabolism - also impairs Neutrophil host defenses - thus patients not tolerate pulmonary infexn well - surfactant accumulation w/in alveoli results in V/Q mismatch and hypoxemia - can see lymphocytosis - usually presents in 3rd – 4th decade of life - 2 x as common in men Clinical features: i. insidious onset ii. diffuse bilateral lung infiltrates iii. occasional hemoptysis/fever iv. Clubbing is NOT a feature - can be seen as early as 8 years of age

Answer 165

i. Whole lung lavage – current standard; works well for most patients; improves survival/QOL; if late in course can become less effective ii. Small series of GM-CSF augmentation being effective –not looked at prospectively evaluating indications/timing/route/duration etc and so more studies required iii. Rituximab – small number of patients shown to be effective – requires more studies

Answer 166

- results from deleterious variants of gene encoding the alpha-chain of GM-CSF receptor (CSF2RA) Found on X and Y chromosomes - phenotypic variability demonstrated: age of presentation between 1 – 10 years, symptoms of dyspnea and fatigue of varying amounts, no auto-Ab’s, elevated serum GM-CSF

Answer 167

- CSF2RA genetic testing for mutation; also CSF2RA protein testing (absent in many) - assess signaling induced by GM- CSF - serum GM-CSF (would be elevated)

Answer 168

- symptomatic patients receive whole lung lavage with variable ranges of time between (months to more then 2 years) - Likely no response to GM- CSF, as levels already high and receptor is abnormal

Answer 169

Genetic defect in CSF2RB can cause phenotype of PAP - Due to abnormality in GM-CSF receptor abnormality - have increased GM-CSF and no auto-Ab’s - mechanism of PAP in lysinuric protein intolerance (LPI) not known; likely b/c abnormal alveolar macrophages as seen to recur in patient with PAP in LPI post heart-lung Tx suggesting it’s macrophage and not AEC2 and deficient surf - of note, no genetic defects in GM-CSF production itself has been identified in causing PAP in humans

Answer 170

- Although thought no response to GM-CSF if the receptor is abn - However if issue of binding affinity, more GM-CSF may help – trials w/inhaled GM- CSF underway - Until then – whole lung lavage is mainstay - Bone Marrow therapy may be curative (as macrophages are bone marrow derived)

Answer 171

1. Genetics 2. Lung histopathology 3. Lung/serum biomarkers

Answer 172

38 weeks, male, operative delivery and white race – absence of these or failure to improve w/in 7 – 10 days or FHx severe neonatal lung disease – think surfactant d/o

Answer 173

ABCA3, SP-B deficiency If negative: SP-C, NKX2-1

Answer 174

NKX2-1 If negative: ABCA3, SP-C

Answer 175

SP-C, ABCA3 (later = also SP-C) if negative: NKX2-1, SP-B (early onset)

Answer 176

CSF2RA/B if negative: SP-C, SLC7A7

Answer 177

FOXF1 - autosomal dominant - Rare, generally lethal - Early postnatal respiratory distress, PPHN (not responsive to typical treatment) - Usually have other manifestations: - Cardiac (HLH) - GI (malrotation, atresia) - Renal - Usually term/near-term - Presentation identical to PPHN - Does not respond to therapy (Ie iNO, ECMO), or only responds transiently

Answer 178

Normal, with subsequent development of hazy opacity

Answer 179

- Pulmonary veins running along pulmonary arteries (essential to diagnosis) - Reduction/absence of veins in intralobular septa - Muscularization of pulmonary arteries/arterioles - Reduced density of capillaries in alveolar walls - +/- lobular architecture simplification with lymphangiectasia

Answer 180

Thought to be caused by abnormalities in the FOXF1 gene (haploinsufficiency - loss of 1 gene, so loss of function) - Associated cardiac and GI anomalies are due to haploinsufficiency of FOXC2 and FOXL1 - Unclear whether the arterial and lobular abnormalities are primary or secondary to vein misalignment. - May have artery hypertrophy secondary to deficient lobular development and poor gas exchange with hypoxemia

Answer 181

Clinical Hx: - Severe hypoxemia and idiopathic pulmonary hypertension, with no anatomic cause Biopsy: - Hx is supportive, but diagnosis is established only with biopsy. - Biopsy is limited by subtle findings, and if limited sample of lung obtained, or if disease is patchy

Answer 182

Surfactant metabolic abnormalities (SFTPB, ABCA3), PIG, Lymphangiectasia Distinguish from disorders of lung development (Ie Congenital Alveolar dysplasia, pulmonary hypoplasia) - These diseases may have lobular simplification and vascular changes, but will NOT have misalignment of pulmonary veins

Answer 183

Supportive (ventilation, iNO, ECMO) - Do not provide long term survival, longest is 101 days - Lung transplant attempted - Given grave prognosis, establishing diagnosis with lung biopsy or at autopsy is recommended

Answer 184

Occur in vast context: prematurity, prenatal pulmonary hypoplasia, Congenital heart disease, Chromosome abnormalities (T21), and normal children with early postnatal injury In general, clinical severity out of proportion to known comorbidities/circumstances

Answer 185

- Oligohydramnios (PROM, renal obstruction) - Restriction of thoracic volume (space occupying lesion/deformities) - CNS and/or neuromuscular disorders → reduced fetal breathing - Prem related BPD - CHD - Poor pulmonary blood flow (TET) - Cyanotic disease with impaired alveolarization - Chromosomal Abnormalities - T21 (impaired postnatal alveolarization) - Other

Answer 186

Variable, based on etiology, age, severity of abnormality. | - Subpleural cysts are often seen in pulmonary hypoplasia associated with T21

Answer 187

Lung weight to body weight is most reliable parameter of lung growth (esp in prems) Radial Alveolar count - Number of transected alveoli with line drawn perpendicular from the center of a bronchiole - Normal = 5 alveolar spaces - Requires standard inflation (radial alveolar count is reduced in uninflated lungs) - Reduced in pulmonary hypoplasia, often with prominent bronchovascular structures, widened interstitium May see lobular simplification with alveolar enlargement with poor alveolarization of postnatal onset (more common in sub-pleural space) - PIG is a frequent finding in biopsies with impaired lung growth

Answer 188

Prenatal and postnatal insults can impact lung maturation/development - Requires distention with liquid and fetal respiratory movements for growth - Anything that impairs this can cause prenatal growth disorder - Range of severity, depending on mechanism of hypoplasia, and timing of insult - If early insult (< 16 wks GA), may affect branching and acinar development - Ie. renal, CDH - If later (PROM), will affect acinar development only - Postnatal abnormalities impact late alveolarization (typically subpleural) - Multiple factors likely play a role (hypoxia, abnormal pulmonary blood flow)

Answer 189

Broad - Other abnormalities of lung development (lymphangiectasia, ACD/MPV), PIG, Surfactant production/metabolism - Alveolar enlargement is often misinterpreted as emphysema or consequence of lung injury/remodeling - No evidence of destructive process/fibrosis

Answer 190

Supportive care - Treatment of underlying conditions (this drives prognosis) - Increased morbidity and mortality when compared to other causes of diffuse lung disease - 34% mortality in the chILDRN study - Prematurity and Pulm Hypertension were predictors of mortality - Highest mortality with high degree of alveolar enlargement and simplification (severe lung growth abnormality) ~ 80% mortality

Answer 191

Only in neonates/young infants - Typically become symptomatic in first few days to weeks of life, after initial “well period” - PIG is often self limited, typically not diagnosed after 6 months of age - Variable presentation - From tachypnea/hypoxia to neonatal respiratory failure and pulmonary hypertension - Term or preterm infants affected - Often seen with other lung growth abnormalities (Ie chronic neonatal lung disease of prematurity, pulmonary hypoplasia, congenital heart disease, pulmonary hypertension, meconium aspiration etc)

Answer 192

Diffuse infiltrates/hazy opacities on CXR | - No common CT changes

Answer 193

AKA cellular interstitial pneumonitis - Increased glycogen laden mesenchymal cells in alveolar interstitium - Biopsy: patchy or diffuse expansion of alveolar walls by “bland spindle shaped cells” (pale/bubbly cytoplasm) - There is no inflammation or fibrosis in interstitium - Strong positive for Vimentin (mesenchimal marker) - May be PAS stain positive (PAS = Periodic acid Schiff) Fixatives will affect the preservation of glycogen, therefore PAS staining may be hard to demonstrate. - EM is the best approach to reveal accumulation of glycogen in interstitial cells

Answer 194

Most present within first 24 hours of birth, most with hypoxia at birth - chILDRN study found that patchy PIG was found in ~ 40% of cases with lung growth abnormality (Ie. prematurity associated chronic lung disease, pulmonary hypoplasia, Trisomy 21, Congenital Heart Disease) and with vascular disorders mimicking ILD - Rare to see in children > 6 months

Answer 195

Accumulation of mesenchymal cells in interstitium may represent changes in the maturation of the pulmonary mesenchymal cells, versus proliferation of the mesenchymal cells for some reason

Answer 196

Only diagnosed with lung biopsy - Diagnosis supported by neonate with respiratory compromise, especially when the severity of disease is disproportionate to degree of other conditions

Answer 197

Sepsis, CHD, Lung development disorder (ACD/MPV), Pulm hypoplasia, Pulmonary vascular disease, lymphangiectasia, surfactant production/metabolism - PCD (frequently causes neonatal tachypnea/resp distress)

Answer 198

Treatment is supportive (supplemental O2, occasionally mechanical ventilation, Pulmonary hypertension treatment) - Mortality is rare (tends to be related to complications) - Mortality is increased when pulmonary conditions occur with PIG - Consider use of high dose pulse steroids (case report data) - Consider the impact on postnatal alveolarization and neurodevelopment

Answer 199

Rare disorder - Otherwise healthy term/near-term infants - Present with tachypnea and retractions (generally insidiously) within the first few months to year of life - Crackles are prominent, hypoxemia is common - Rare to have wheeze - May develop FTT - Exacerbations with URTI - Infant PFTs: profound air trapping, reduced FEV0.5 and FVC, elevated FRC, RV, and RV/TLC

Answer 200

May be normal, May show hyperinflation CT is distinctive: - Ground glass opacities centrally, and in RML and lingula - Air trapping/mosaic appearance

Answer 201

Lung biopsies often show minimal to no pathologic changes - Pathologic diagnosis rests on finding increased proportion of neuroendocrine cells within airways - Identified with bombesin and serotonin immunostaining - 2 airways with more than 10% bombesin positive areas or cell numbers of the airway suggest diagnosis - Need adequate sample (10-15 airways), often with multiple biopsy sites due to wide variability

Answer 202

Familial cases with affected siblings have been described (? genetic predisposition) - Unknown whether the neuroendocrine cells are a marker of NEHI, or involved in pathogenesis - Recent evidence looking at # of NE cells and severity suggests causal role - Thought that NE cells play role in oxygen sensing and airway/arterial tone → ? NEHI leads to VQ mismatch

Answer 203

Exclude more common causes - Infection, CF, CHD - Lung biopsy is considered definitive diagnostic approach - Pathologic interpretation should be interpreted by physician with experience in this field - Given advances, many diagnoses are occurring without use of biopsy - Important to know that NE cells are also seen with other conditions (BPD, SIDS, Pulmonary Hypertension, CF) DDx: Acute/chronic infection, asthma, airway injury, Bronchiolitis obliterans Pulmonary hypoplasia, PIG, Surfactant production/metabolism disorders

Answer 204

BPD SIDS Pulmonary Hypertension CF

Answer 205

Supportive Care - Supplemental Oxygen, supplemental nutrition - Corticosteroids are not helpful in most cases - No deaths reported with this condition, no patients have required lung transplantation - Most children show overall improvement - Children may show symptoms with resp infections or exercise

Answer 206

Alveolar Simplification/impaired postnatal alveolarization Subpleural cysts Cystic Dilatation of alveoli, with hypertensive changes of pulmonary vasculature

Answer 207

- Pleuritis (especially with pericarditis). Consider SLE if isolated pleuritis and arthritis. - Pneumonitis - Interstitial reticular and nodular infiltrates - Bronchiectasis - Vasculitis/diffuse alveolar haemorrhage (DAH) - PHT - Lipoid pneumonia – from endogenous lipid - BO 50% of asymptomatic pts have abnormal PFTs (usually restrictive) – muscle weakness evident by MIP & MEP -50% of MAS have lung involvement (25% ventilated) = infiltrates, pneumonitis, edema, haemorrhage.

Answer 208

- Pulmonary haemosiderosis | - Lymphoid follicular bronchiolitis

Answer 209

- NSAIDs, MTX, TNF- a inhibitors (etanercept, adalimumab, infliximab), steroids, IL-1 antagonists (anakinra), IL-6 antagonist (toclizumab) - Acute serositis = pulse steroids - MAS = anakinra, cyclosporine - MTX shown to not increase risk of pulmonary disease in children with arthritis.

Answer 210

- Pleuritis/pleural effusion exudate (9-32%) - Acute pneumonitis is rare – fever, dry cough, dyspnea, pleuritic chest pain, tachypnea. - CXR: infiltrates. - Chronic ILD is extrememly rare – exertional dyspnea, cough, pleuritic chest pain, basal crackles. Usually with multisystem SLE. - Pulmonary haemorrhage – usually w/lupus nephritis, concurrent infection. - PHT (esp. if lupus anticoagulant or Raynaud’s) - PE with antiphospholipid Ab - Shrinking lung syndrome = dyspnea, pleuritic chest pain, tachypnea, CXR reduced volumes, raised diaphragms, basal atelectasis, PFTs restrictive. ?due to diaphragmatic dysfunction. >1/3 have abnormal PFTs, usually restrictive +/- diffusion. Pleuritis was found to occur more frequently in patients with a younger age at disease onset, and longer disease duration, who manifested more cumulative disease-related damage, and in those who had positive anti-Sm and anti-RNP antibodies

Answer 211

Chronic ILD: alveolar wall thickening, interstitial fibrosis, interstitial lymphocytic infiltrates, granular deposits of Ig and Complement.

Answer 212

-Corticosteroids for pleuritis. -Pulsed steroids for pulmonary haemorrhage. Long-term morbidity includes premature atherosclerosis and osteoporosis.

Answer 213

- ILD: irregular linear opacities with consolidation and ground- glass attenuation. - Pneumomediastinum - Aspiration pneumonia - Hypoventilation - Acute interstitial pneumonitis and BOOP - Abnormal PFTs in 30-40% - Muscle weakness

Answer 214

Anti-Jo-1 Ab Reduced MIP & MEP Normal DLCO and increased RV without decreased FEV1/FVC - helps to distinguish respiratory muscle weakness from ILD

Answer 215

High dose steroids Cyclosporine Cyclophosphamide RItuximab

Answer 216

- ILD (80%) – dyspnea, dry cough. - CXR – ground-glass, reticular pattern, traction bronchiectasis. - PAH (4-9%) - Pleuritis and pleural effusions - Bronchiectasis - BOOP - Alveolar hemorrhage - Spontaneous pneumothorax with severe fibrosis - Aspiration pneumonia with GERD - Abnormal PFTs in 42-65% (restriction/diffusion) ILD, PAH, and cardiomyopathy are dreaded organ manifestations associated with mortality in children

Answer 217

ILD - nonspecific interstitial pneumonitis.

Answer 218

Cyclophosphamide, other immunosuppressants

Answer 219

- Fibrosis* - Pleural effusions* - PAH* - PE - Pulmonary hemorrhage - Diaphragmatic dysfunction - Aspiration pneumonitis It is characterized by the presence of high titer anti-U1 ribonucleoprotein (RNP) antibodies in combination with clinical features of SLE, SSc, or DM

Answer 220

- Intrathoracic LN - Parenchymal dz - Dyspnea, wheeze, cough - Parenchymal infiltrates may be nodular, fibrotic, or alveolar and tend to occur in the upper lobes. - Pleural effusion, pneumothorax, pleural thickening, calcification, and atelectasis also have been reported. ``` Staging: 0 = nl (10% at presentation) I = bilateral hilar adenopathy II = BHL with parenchymal infiltrates (71%) III = parenchymal infiltrates without BHL (8.3%) IV = fibrosis -Pleural effusion -Pneumothorax -Pleural thickening -Calcification -Atelectasis ``` PFTs nil if stage 0/I – restrictive/diffusion, sometimes obstructed.

Answer 221

- Bronch = waxy yellow mucosal nodules, erythema, edema, granularity, cobblestoning of mucosa, bronchial stenosis. - BAL lymphocytosis >85%; increased CD4:CD8 ratio (opposite in ILD with connective tissue disease). - Diagnosis = typical clinical features + noncaseating granulomas on biopsy.

Answer 222

- Spontaneous remission in many | - Stage III likely to progress to fibrosis so most treated with steroids.

Answer 223

- Dyspnea, cough, hypoxia (19%) - DAH - Subglottic stenosis - Upper airway: sinusitis, nasal septal ulceration/perforation, otitis media, mastoiditis, hearing loss, oral ulcers, nasal cartilage damage, saddle-nose deformity. - CXR = nodules, fixed infiltrates, cavitations, mediastinal LN, effusion, pneumothorax.

Answer 224

Anti-PR3 | ANCA

Answer 225

- Bronch: mucosal erythema, ulceration, hemorrhage, cobblestoning, nodules, polyps, submucosal tunneling, synechial bands, airway stenosis. - Lung biopsy yield is low as disease is patchy.

Answer 226

- Steroids and cyclophosphamide | - Obstructing airway lesions: intralesional steroids, surgical.

Answer 227

Pulmonary hemorrhage (30- 50%) – presents likely IPH

Answer 228

- Anti-50%) – presents likely IPH myeloperoxidase (MPO) - ANCA - No granulomas

Answer 229

- Migrating pulmonary infiltrates vs fixed infiltrates like Wegener’s - Concomitant severe atopic asthma or allergic rhinitis (almost 100%)

Answer 230

Granulomatous

Answer 231

- Dry cough, obstruction, AHR - ILD is rare -ILD – LIP

Answer 232

- Abnormal PFTs (diffusion) - Bronchiectasis - reduced DLCO (most common) - bronchial hyper-reactivity - bronchiectasis (most common in adults) -rare: tracheal stenosis, colobronchial/ileobronchial fistulaue, BO, granulomatous pulmonary nodues, pulmonary vasculitis, pleural effusions, BOOP

Answer 233

Noncaseating epithelioid cell granulomas The granulomas consist of tightly organized collections of predominantly CD4+ T lymphocytes and mononuclear phagocytes (epithelioid cells, macrophages and multinucleated giant cells). In the lung, most granulomas are located in the perilymphatic areas, including near bronchioles, in the subpleural space, and the perilobular spaces The granulomatous lesions usually heal with preservation of lung parenchyma; however, in 20% to 25% of patients, fibroblasts proliferate at the periphery of the granuloma and produce fibrotic scar tissue.

Answer 234

A triad of acute arthritis, bilateral hilar adenopathy (BHL), and erythema nodosum is a common presentation in 9% to 34% of adults but is less common in children.

Answer 235

1) Immunodeficiency syndromes (especially chronic granulomatous disease) 2) Fungal and mycobacterial infections, berylliosis, 3) Ulcerative colitis 4) Wegener's granulomatosis

Answer 236

1. Pulmonary sarcoidosis: Worsening pulmonary symptoms, deteriorating lung function, progressive radiographic changes (worsening of interstitial opacities, cavitation, progression of fibrosis with honeycombing, development of pulmonary hypertension). 2. Cardiac, neurologic, ocular, renal involvement or hypercalcemia, even with mild symptoms, because fatal arrhythmias, blindness, and renal failure may develop. 3. Severe debilitating symptoms from any organ involvement Therapy is not indicated in asymptomatic children with stage I or II pulmonary disease with normal or mildly abnormal lung function. Stage III disease needs to be followed closely because adult data suggest that the majority do not resolve, it may progress to pulmonary fibrosis, and most patients will require therapy in the future.

Answer 237

Corticosteroid dosing typically is started at a relatively high dose (1 mg/kg/day depending on severity of disease) for 4 to 6 weeks and then is tapered. - A response to therapy is usually seen within 6 to 12 weeks of initiation of therapy, with improvement in symptoms, pulmonary infiltrates, and lymphadenopathy on imaging and variable improvement in pulmonary function. - Steroid needs to be continued for 12 to 18 months in order to prevent relapse of disease. Steroid sparing agents: - Methotrexate - Hydroxychloroquine - Infliximab - Lung transplant for severe cases

Answer 238

Erythema nodosum has been associated with a good prognosis while central nervous system involvement is associated with a poor prognosis.

Answer 239

``` Infection Air leak Upper airway obstruction esp.GPA Acute pneumonitis or pleuritis DAH PE Progression of CLD Cardiac dysfunction ```

Answer 240

``` Generalized muscle weakness Deconditioning Cardiac Disease Thromboembolic disease Opportunistic infection Drug toxicity effects Inflammatory lung disease ```

Answer 241

Restrictive defect with low MIPS/MEPS and low peak flow in more severe disease DLCO preserved until severe loss of volume With severe disease, hypoventilation results in hypercapnia and hypoxia with norma A-a gradient

Answer 242

Obstructive defect DLCO preserved until severe end stage disease With end stage disease - hypoxia at rest

Answer 243

Variable pattern but often restrictive DLCO increase if hemorrhage is recent During active bleeding, hypoxia often profound with a wide A-a gradient

Answer 244

Normal PFTs Reduced DLCO Hypoxia at rest even with moderate pulmonary HTN

Answer 245

Restrictive defect, often severe DLCO less reduced than expected for degree of restrictive defect Hypoxia at rest or with exercise is frequent

Answer 246

Lung infiltrates Pneumonitis Pulmonary hemorrhage Pulmonary edema (which may result from myocardial dysfunction associated with the hypercytokinemia)

Answer 247

Infection SLE is associated with an increased risk of a wide range of infections, including bacterial, viral, mycobacterial, fungal, and parasitic infections, with the respiratory tract as one of the common sites In addition immunosuppressive treatments to control the disease confer an increased risk of opportunistic infections such as pneumocystis, cytomegalovirus, and fungal infections.

Answer 248

Alveolar wall thickening, Interstitial fibrosis Interstitial lymphocytic infiltrates Granular deposits of immunoglobulin and complement.

Answer 249

Pulmonary vasculitis Pulmonary thromboembolism ILD Valvular heart disease.

Answer 250

Pulmonary embolism

Answer 251

Associated with SLE Typically presents with progressive dyspnea, pleuritic chest pain, and tachypnea. Chest radiographs may demonstrate reduced lung volumes, raised hemidiaphragms, and basal atelectasis PFTs are usually restrictive.

Answer 252

1. ILD (may be Rapidly progressive) a. BOOP b. Pulmonary fibrosis c. DAD 2. Pneumomediastinum a. is a characteristic complication of adult DM with interstitial pneumonitis and has also been reported in JDM 3. Aspiration pneumonia 4. Hypoventilation

Answer 253

GPA (formerly Wegener’s), Microscopic polyangiitis (MPA), Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss) Isolated pulmonary capillaritis ANCA-associated vasculitis (AAV) syndromes are characterized by necrotizing vasculitis of small vessels, frequent pulmonary and renal involvement, and a paucity of immune deposits in the blood vessel wall.

Answer 254

ANCA-associated vasculitides Goodpastures syndrome SLE Thromboembolic disese Infections

Answer 255

*Nodules (90%) followed by fixed infiltrates (45%) ▪ Nodules tend to be multiple, greater than 5mm in diameter and cavitating in 17% Airspace opacification usually correlated with clinical evidence of pulmonary hemorrhage ▪ Granulomatous lesions (necrotizing) Ground glass opacification on CT (52%) Pulmonary cavitations Mediastinal lymphadenopathy Pleural effusions Pneumothoraces

Answer 256

Mucosal erythema, edema, ulceration, hemorrhage, cobblestoning, nodules, polyps, submucosal tunneling, synechial bands, and airway stenosis Endobronchial findings nonspecific, similar findings encountered with infections and sarcoidosis

Answer 257

Subglottic stenosis

Answer 258

Infections (especially mycobacterial, fungal, or helminthic infections in addition to common viral and bacterial causes), Other causes of pulmonary-renal syndrome (other ANCA-associated vasculitides, SLE, MCTD, Goodpasture syndrome) Sarcoidosis, UC with pulmonary involvement Malignancy Chronic granulomatous disease

Answer 259

Small airway disease caused by injury leading to fibrosing and narrowing or complete obliteration

Answer 260

Causes: inhalation of toxins (hydrochloric acids); Inflammatory disease (SLE); post BMT or lung tx, infection Focusing on post-infectious BO → leading cause is adenovirus (serotypes 3, 7, 21 have highest virulence); influenza, parainfluenza, measles, RSV, HMNV, varicella, mycoplasma Initial presentation like bronchiolitis with fever, cough, wheeze, dyspnea and CXR showing peribronchial thickening and patchy bronchopneumonia with collapse/consolidation

Answer 261

Hospitalization > 30 days, multifocal pneumonia, hypoxia, hypercapnea, PICU stay, need for mechanical ventilation

Answer 262

Will have incomplete recovery of symptoms → may develop recurrent pneumonia, hyperinflation, bronchiectasis, Swyer-James syndrome

Answer 263

Airflow obstruction with decreased FEV1, FEV1/FVC, mid-expiratory flow rates lung volumes show increase RV and RV/TLC

Answer 264

High WBC with increased neutrophils and lymphocytes with decreased CD4/CD8 ratio

Answer 265

HRCT shows mosaic perfusion, vascular attenuation, and expiratory air trapping (also can see bronchiectasis and atelectasis)

Answer 266

Typical clinical hx 0-4 Documented adenoviral infection 0-3 HRCT showing mosaic perfusion 0-4 Score ≥ 7 predicted dx of BO with 100% specificity and 67% sensitivity but score < 7 did not accurately rule out dx

Answer 267

Lung bx is gold standard for dx but because heterogenous disease, sampling is a problem

Answer 268

Inflammation of small airways → predom CD8 T lymphocytes filling the lumen of the small airways Fibrous tissue creating varying degrees of luminal occlusion in the small airway (can have total obliteration of the lumen by fibrotic tissue) Note the proliferative type characterized by granulation tissue plugs (masson bodies) now is called BOOP = COP

Answer 269

Supportive care: O2, nutrition, avoid smoke/irritants, vaccinations, treat GER ▪ Small number improve with bronchodilators and ICS ▪ Systemic steroids- pulse dosing 30 mg/kg x 3 days, if deemed beneficial then repeat monthly x 3-6 mos ▪ Azithromycin

Answer 270

Pulmonary lymphatic system composed of two interconnected pathways: 1) one drains the subpleural space and outer surface of the lung 2) the other follows bronchovascular bundles to drain the deeper portions of the lung

Answer 271

1) Disordered Embryonic Development - plays a role in pulmonary lymphangiectasia - often presenting in the neonatal period 2) Disorders of Lymphatic Growth - Presenting outside the neonatal period - ie. lymphangiomatosis

Answer 272

Dilatation of pulmonary lymphatic vessels and disordered drainage = accumulation of lymph in lungs (spectrum of respiratory disease) Most present neonatal period or infancy Primary = abnormal lymphatic development (failure of regression of large lymphatic vessels) Secondary = Obstructive process impeding lymph drainage Chromosomal disorders associated: Noonan syndrome, Hennekam syndrome, Yellow Nail syndrome, Down syndrome o More likely to have generalized disease

Answer 273

At birth develop respiratory distress → to respiratory failure. Can have chylous effusions but some do not have effusions. Later in infancy or childhood present less severe: chronic tachypnea, recurrent cough, wheezing. PL has been associated w/ chylothorax, chylopericardium, and chylous ascites.

Answer 274

CXR, high res. CT (thickening of peribronchovascular septa and septa surrounding lobules.) ``` Lung biopsy (gold standard - dilated lymphatic vessels in interlobular septa, near bronchovascular bundles, and/or within the pleura) Extrapulmonary disease manifestations: GI involvement, bony disease, or skin lesions from draining lymphatic glands. ```

Answer 275

No cure, supportive tx iNO, ECMO used with variable success Natural course is variable; a high mortality rate if diagnosed in neonatal period. Those who survive the neonatal period seem to eventually experience improvement of disease

Answer 276

Lymphangiomatosis = multiple lymphangiomas (less common) | o Affects multiple organs (liver, soft tissue, spleen, bones, mediastinum, lungs).

Answer 277

Syndrome characterized by chylothorax, bone cysts, lymphangioma on biopsy - Chylothorax = worse prognosis - Proliferation of vascular structures in bone - Symptoms of cough, dyspnea, pain Gorham-Stout disease and lymphangiomatosis both occur sporadically without a known inheritance pattern

Answer 278

Disease of thorax can manifest in mediastinum, pleural space, chest wall, lungs or pericardium May present with cough, chest pain, dyspnea, wheezing Chylous effusion usually prominent

Answer 279

CXR - interstitial infiltrates, chest mass, effusions, or bony lesions. HRCT - multiple lymphangiomas, smooth thickening of interlobular septa and bronchovascular bundles, ground-glass attenuation, or effusions Biopsies of lesions - increased numbers of dilated lymphatic channels

Answer 280

Natural history = progressive growth of lymphangiomas that eventually compress vital structures. Young age and respiratory involvement predict poor outcome Therapy for severely symptomatic pleural effusions may include thoracentesis or pleurodesis. When lymphangiomas are diffuse, complete surgical resection not possible. Interferon-alpha 2b reported to halt lymphatic proliferation o Consider this for Gorham stout disease as well

Answer 281

Abnormal smooth muscle proliferation, cystic destruction in lung ● Typically childbearing years ○ recurrent pneumothoraces, dyspnea, lung cysts ● +/- chylous effusions ● Differentiated from lymphangiomatosis based on presence of lung cysts and immunohistochemistry ● May be associated with Tuberous Sclerosis (40% of women with TS)

Answer 282

Deposition of Ca phosphate calculi within alveoli - related to disordered phosphate transfer - Type II alveolar cells degrades surfactant. Phosphate is a waste product of this. May build up in cells unless properly removed. Phosphate reuptake secondary to dysfunction of the SLC34A2 gene product causes formation of calcium phosphate microliths Diff dx includes: sarcoidosis, TB, histoplasmosis, IPH Autosomal Recessive

Answer 283

Most asymptomatic, incidental finding or relative w/ finding. Sx: dyspnea, cough, chest pain in only 1/2 of those affected. At diagnosis, PFT usually normal; declining function occurs over decades

Answer 284

CXR –“Sandstorm” appearance; sandlike Ca-Phosphate micronodules - denser at lung bases CT - micro nodules, ground-glass opacities, subpleural interstitial thickening, interlobular septal thickening

Answer 285

Lack of consensus regarding natural course Reports describe development of pulmonary fibrosis followed by respiratory insufficiency, pulmonary HTN, death secondary to respiratory failure over decades after dx No cure for PAM. Lung tx successful in past

Answer 286

Most common lysosomal storage disease Mutation glucocerebrosidase gene = buildup of glucocerebroside Glucocerebroside accumulates in macrophages = Gaucher or foam cells. Infiltration of Gaucher cells may occur within alveoli, within interstitial spaces, around airways, or within pulmonary vasculature (infiltrative lung disease) Autosomal Recessive

Answer 287

Clinical pulmonary disease uncommon but pts have abnormal PFT Hepatopulmonary syndrome may also occur secondary to the liver disease

Answer 288

CXR - reticulonodular changes | CT -ground-glass consolidation, interstitial involvement, alveolar opacities, bronchial wall thickening

Answer 289

Enzyme replacement therapy decreases organomegaly, less successful in reversing existing pulmonary disease. ERT may slow or prevent progressive decline in lung function. Role of ERT in preventing lung disease not known.

Answer 290

- Deficiency of acid sphingomyelinase = accumulation of sphingomyelin within cells/ tissues - In lung, build-up of foam cells containing sphingomyelin in alveoli, alveolar walls, lymphatic spaces, pleural space -Rarely, severe form of ILD may present in infancy or early childhood - In many cases, ILD more indolent, and survival into adulthood AR

Answer 291

- Presentation w/ hepatomegaly, splenomegaly, thrombocytopenia, dyslipidemia. - Many also have ILD - No neurologic involvement and often survive into adulthood

Answer 292

PFTs: decreased FVC, FEV1, and diffusing capacity CT - ground-glass appearance, reticulonodular densities, thickening of interlobular septa, thickening of intralobular lines.

Answer 293

- No specific tx exists - Whole lung lavage tried with varying results - ?Future for enzyme replacement therapy

Answer 294

- Thoracic involvement: neurofibromas (often plexiform) can arise from the chest wall or posterior mediastinum - Can surround vital structures -Malignant transformation can occur so consider bx - Also associated with ILD - Diffuse lung disease mainly in adult; not reported in children AD

Answer 295

ILD appears as large, apical thin-walled bullae and basilar fibrosis

Answer 296

Pulmonary fibrosis

Answer 297

AAT inhibits enzymatic breakdown of lung tissue; dysfunction can lead to severe obstructive lung dz One of most common inherited diseases worldwide but pulmonary manifestations of AAT deficiency is very rarely in children Inherited in co-dominant manner >100 variants of the protein identified Classification based on protease inhibitor (Pi) system - F = Fast - M = Medium - S = Slow - Z = Very Slow - AAT inhibits proteolytic enzymes (trypsin, neutrophil elastase, collegenase, macrophage cathepsin) - Co-dominant expression of both alleles determines serum level of AAT, level determines risk of disease Not all at risk individuals develop disease, environmental factors influence: AAT deficiency and smoking = accelerated rate of disease development Exposure to kerosene heaters, employment in agriculture, exposure to other pollutants from biomass fuel sources: all implicated in emphysema Deficiency also causes liver disease (ranging from mild elevation of LFTs to cirrhosis & hepatic failure)

Answer 298

Pulmonary vasculitis can lead to hemorrhage, infarction, death -Lung disease in adults, reported in kids Pulmonary artery aneurysms is most common resp presentation of dz (single or multifocal) Present w/ hemoptysis Pulmonary parenchymal dz also reported and associated w/ pleuritis, reticulondular or focal opacities, mass lesions, hilar enlargement; findings occur most likely secondary to hemorrhage, infarction related to pulmonary vasculitis

Answer 299

Whole lung irradiation for e.g. mets to the lung (Wilm’s tumor, sarcomas, hepatoblastoma) Total body irradiation for e.g. preconditioning - Acute pneumonitis – usually 30 to 90 days after tx with cough, dyspnea, hypoxemia and pleuritic pain - Rx systemic steroids - Imaging = Diffuse ground glass densities Chronic fibrosis – appear 6 to 24 mos after tx, usually but not always proceeded by pneumonitis symptoms, most commonly presents with progressive dyspnea - Imaging = Streaky densities, decreased lung volume or atelectasis, pleural thickening Impair growth of bone, cartilage and muscle of thorax

Answer 300

Bleomycin, Dactinomycin have additive toxicity to radiation - can lead to pulmonary fibrosis Actinomycin D, adriamycin cause radiation recall with delayed presentation of toxicity up to 6 weeks later Busulfan, Cyclophosphamide, Methotrexate are other pulmonary toxins

Answer 301

1. Pulmonary edema, pleural effusions, ARDS 2. Diaphragm dysfunction → resp distress, atelectasis, pneumonia 3. Medication toxicity 4. PTLD

Answer 302

Immunosuppression → T lymphocyte depletion → uncontrolled EBV driven B cell proliferation → range from polyclonal B lymphocyte expansion to B cell lymphomas Most common pulmonary PTLD sx: cough, dyspnea and upper airway obstruction Imaging shows nodules but can also see LN, consolidations or effusion Should biopsy and assess for EBV-early RNA (EBER) – staining cells Median onset is within 24 mos of transplant Spectrum from polymorphic – monomorphic (worst prognosis)

Answer 303

Seroconversion of EBV-naive recipient, high degree of immunosuppresion, Rh factor negativity, Rh mismatch, recipient CMV seronegativity

Answer 304

Tx is reduction of immunosuppresion (but may end up with graft rejection) +/- Rituximab, antivirals ``` Tx: reduce immunosuppresion, anti-CD20 agent (rituximab – if CD20 + histology), CHOP chemoTx (cyclophosphamide, prednisone) ```

Answer 305

mTOR drugs (sirolimus and everolimus) – can cause interstitial pneumonitis (but less nephrotoxic than calcineurin inhibitors) Fever, dry cough, dyspnea with exertion, restrictive pattern on pfts Imaging shows interstitial infiltrates, consolidation or ground glass opacities with lower lobe predominance BAL/Bx show lymphocytic alveolitis, pulmonary hemorrhage and organizing pneumonia Tx by stopping the med

Answer 306

1. Hx/PE 2. CXR and HRCT 3. PFTs: spirometry, lung volumes, DLCO, MIPs/MEPs 4. 6 minute walk test

Answer 307

``` Oral mucositis Pulmonary edema PVOD Diffuse alveolar hemorrhage Idiopathic pneumonia syndrome Peri-engraftment RDS ```

Answer 308

2 mos and beyond

Answer 309

ILD - COP PTLD BO chronic GVHD

Answer 310

Bimodal peak: 2 weeks and 6-7 weeks post Clinical signs: dyspnea, non-productive cough, hypoxemia, crackles PFT: restrictive pattern and CXR: diffuse infiltrates BAL cultures neg (2nd BAL recommended 2-14 days after first)

Answer 311

Patchy areas of consolidation with polypoid plugs of loose organizing connective tissue in the respiratory bronchioles and alveolar ducts

Answer 312

``` Hospital/Community acquired pneumonia Fungal pneumonia Aspiration pneumonitis/pneumonia Idiopathic Pneumonia syndrome TB/NTM DAH ARDS Pulmonary edema TRALI ```

Answer 313

``` Discrete Fungal infection Nocardia infection Metastatic calcification PTLD Malignancy Septic emboli Tree-in-bud pattern Viral pneumonia Bacterial pneumonia BOS ```

Answer 314

``` Pulmonary edema TRALI ARDS DAH CMV PJP Common viruses Drug toxicity ```

Answer 315

``` Air trapping BOS Viral infection Vascular disease Pulmonary HTN/porto-pulmonary HTN Venous thromboembolism ```

Answer 316

Lower prevalence of end-stage pulmonary disease in children Improved CF care Lower procurement rate of donor lungs Small number of pediatric lung Tx centers around world

Answer 317

``` CF – end stage Pulmonary HTN (often times associated with CHD) Neonatal d/o – surfactant protein (B, C, ABCA3) deficiency, ACD ILD BO BPD Pulmonary hypoplasia Re-transplant ```

Answer 318

``` Active malignancy within 2 years Sepsis TB AIDS Severe neuromuscular disease Hepatitis C with histologic liver disease Extenuating social/compliance issues ```

Answer 319

``` Pleurodesis Renal insufficiency Nutritional status (really low or high BMI) Mechanical ventilation Scoliosis Poorly controlled DM Osteoporsis B.cepacia ```

Answer 320

Donor lungs assessed with ABG’s, CXR, inspection, airway C/S, bronchoscopy Donor hx reviewed for acute viral infection and serologies checked (hep A, B, C, HIV, VZV, CMV, EBV, HSV)

Answer 321

Immunosuppression – triple immunosuppression (steroids/calcineurin inhibitor (tacro)/cell cycle inhibitor MMF/AZT) Antimicrobials – IV Abx pre-peri-post transplant targeting recipient microbiology and donor micro (often known post-Tx); if no CF use Abx with good G+/G- coverage, ie. Tazo for 7 – 10 days Septra for PCP proph (nebulized pantamidine is alternative) Nystatin CMV prophylaxis (variable from center to center – often involves some time of gancyclovir/valgancyclovir +/- CMVIg and serial monitoring of CMV PCR) Re: monitoring – may need to use infant/toddler PFT’s; CXR; CT; bronchoscopy and TBBx

Answer 322

Surgical complications: - Bleed (pleural space, at anastomosis) - Phrenic N injury - Dehiscence of vascular/bronchial anastaomosis - Require bronchoscopy surveillance 24-48hours post - Primary graft dysfunction (PGD) Infectious/Immunologic: - Hyperacute rejection - Acute rejection (as early as 1 week) - Infection

Answer 323

Infection (bacterial, viral – CMV, EBV, HSV, fungal) Rejection (acute cellular, humoral (antibody) mediated PTLD (as early as 1 month) Medication side effects

Answer 324

PTLD | Chronic allograft dysfunction - BO/BOS, RAS or simply CAD

Answer 325

Most common problem in first week post-transplant Related to re-implantation lung injury Associated with procurement procedure, duration of ischemia, generation of hydroxyl radicals and pro-inflammatory cytokines during ischemia may be important Characterized by ARDS type picture, DAD on path, marked hypoxemia and pulmonary infiltrates Tx – supportive care

Answer 326

Within hours – rare; potentially catastrophic; associated with circulating recipient Ab’s that bind to donor HLA molecules on vascular endothelium Causes profound graft ischemia – thus cross-match at time of transplant and if positive give plasmapharesis to prevent hyperacute rejection

Answer 327

Acute rejection – can occur as early as 1 week post and as late as 2 – 3 years Lymphocytic attack of graft Symptoms – nonspecific – could be cough, fever, dyspnea, hypoxemia, radiographic change or no symptoms thus routine surveillance bronch with TBBx; Path = perivascular lymphocytic infiltrate Tx = pulse steroids (10 mg/kg methylpred X 3 days)

Answer 328

Can occur later (> 1 month post) from development of donor specific Ab’s (similar to hyperacute, but Ab’s not present at time of transplant, develop over time) Dx criteria not exist; if sick/declining PFT’s/radiographic change and increase DSA (donor specific Ab) then Tx with PLEX +/- steroids +/- thymo +/- IVIG

Answer 329

BO/BOS: 60% at 6 years Leading cause of mortality One form of CAD Dx – from PFT’s, worse function, TBBx showing: obliterated bronchioles with fibrous changes and collagen deposition in the lumen RF’s – episode of acute rejection (particularly occurring > 3 months post-Tx), HLA Ab’s, GERD, respiratory viruses, non-compliance with immunosuppression Tx – AZT 3X/week; thymo, re-transplant

Answer 330

Survival – 50% at 5 years (essentially) Somatic growth is a problem for many patients post-Tx; likely because poor pre-Tx nutrition and use of steroids There is some question regarding whether true lung growth occurs (IE: incr surface area for gas exchange) post transplant. Causes of death: graft failure and infection are No. 1 in first year post; in first 30 days it’s surgical issues; BO is still the biggest obstacle long term

Answer 331

Treatment is supportive and management of the specific underlying disorder. Evacuation of a transudate after the initial diagnostic thoracentesis is indicated only for relief of dyspnea and other cardiorespiratory disturbances caused by mediastinal displacement. Intercostal tube drainage may be provided in lieu of repeated thoracenteses, depending on the child's tolerance of the procedures and the progression of the underlying disorder. Diuretics administered to some patients may slow re-accumulation of the transudate and may decrease or eliminate the need for frequent thoracentesis. Pleural transudates caused by fluid overload (e.g., from intravenous infusion) or overload of lymphatic drainage (e.g., ascites, peritoneal dialysis) may require only diuresis or may resolve spontaneously.

Answer 332

Associated with trauma Requires expansion of vascular volume and direct surgical repair sometimes Thoracotomy indicated when ○ Need more than 20 mL/kg of blood ○ Ongoing blood loss > 3 mL/kg/hour Chest tube always placed to avoid pleural adhesions

Answer 333

1. Drainage of effusion | 2. Nutritional support (MCT to decrease flow of lymph, TPN, surveillance of nutritional status and immune competency)

Answer 334

1. Congenital - Primary lymphagiectasia (syndromes = Noonan's, Turners, Yellow Nail syndrome, Gotham, Milroy) - Lymphangiomyomatosis - Lymphagioleiomyomatosis - Lymphangioma 2. Acquired - Surgical trauma (post CHD surgery, post pacemaker placement, post lung resection, thoracic irradiation) - Blunt thoracic trauma, seat belt injury - Infiltration/mechanical obstruction (Lymphoma) - Intraluminal lymphatic obstruction (Thoracic duct cyst, Thoracic duct thrombosis) - Extraluminal lymphatic obstruction (TB, Sarcoid, Castleman’s disease, Extramedullary hematopoeisis) - Increased venous pressure (CHF, Cardiomyopathy, Constrictive pericarditis, SVC/subclavian vein thrombosis) - Transdiaphragmatic chyle movement (chylous ascites)

Answer 335

○ Appearance: milky, sanguinous, serosanguinous (Does not clear with centrifugation) ○ Exudative effusion by Light’s criteria ○ Lymphocyte predominant (usually > 80% - polyclonal populations of T cells) ○ Triglycerides > 1.24 mmol/L (110 mg/dL) ○ Cholesterol level < 5.18 mmol/L ○ If doubt - can look for chylomicrons on lipoprotein electrophoresis

Answer 336

``` Infection Neoplasm Trauma AI disease Systemic granulomatous disease ```

Answer 337

S. Pneumo (and lesser extent S. Aureus)

Answer 338

Aerobic - S. pneumo - S. aureus - S. pyogenes - H. influenzae type b - E. coli - Klebsiella - Pseudomonas Anaerobic - Microaerophilic strep - Fusobacterium - Bacteroides melaninogenicus - Peptococcus/Peptostreptococcus - Catalase-negative, non-spore-forming, Gram-negative bacilli

Answer 339

Cavitary pneumonia Bronchopleural fistula Pneumothorax Lung abscess (particularly with organisms such as S. aureus) Empyema necessitans when purulent material perforates through the chest wall Fibrothorax, trapped lung ■ Rare in children ■ Total duration on antibiotics: 3-4 weeks per CPS

Answer 340

Male predominance Tall, lean body habitus Cigarette smoking Air leak usually from rupture of apical blebs Connective tissue disorders (Marfan, Birt-Hogg-Dube, follicular gene mutations)

Answer 341

``` Connective tissues disease Airway disease: CF, Bronchiectasis, Acute asthma ILD Post-infectious Malignancy Aspiration of FB Catamenial pneumothorax Congenital pulmonary malformations Neonatal pneumothorax ```

Answer 342

Uncoupling of lung from chest wall Continued airleak can elevate the intrapleural pressure to above atmospheric → tension pneumothorax Leads to: ■ Collapse of ipsilateral lung ■ Contralateral overexpansion → increased retractive forces, pulls mediastinum towards it during expiration → compression of vascular structures → decreased venous return ■ Must generate high intrapleural pressures to ventilate normal lung → worsening ptx → hypoxemia/hypercapnea ■ Tachycardia worsens diastolic filling

Answer 343

Variable symptoms depending on severity of ptx Decreased breath sounds on side of ptx, contralateral shift of heart sounds, Sudden collapse on ventilator with reduced compliance, transillumination of chest in neonates 2 cm distance from lung to chest wall suggests a pneumothorax > 50%

Answer 344

Gas absorption can be hastened by breathing 100% oxygen ■ Washout of nitrogen ■ Increase in venous pO2 ■ pN2 goes to zero, and therefore venous gas pressure is about 617 mmHg less than atmospheric → gradient for reabsorption of gas Large pneumothoraces require intervention - Needle thoracentesis versus chest tube - CT removed when no air leak for 24 hours and tube confirmed in place → can see oscillations of water meniscus with breathing motion (can be hard to appreciate in young children) - Clamp tube before removal - If possible, chest tube removed during exp breath hold Recurrent pneumothorax - Consider pleurodesis - VATS

Answer 345

If persistent or recurrent, consider pleurodesis Withhold PEP during treatment Consider discussion with transplant team

Answer 346

Recurrence of spontaneous ptx common (40-87%) | Increase risk of recurrence if ptx slow to resolve, ongoing cigarette smoking

Answer 347

Respiratory distress syndrome (RDS) Meconium aspiration Mechanical ventilation Congenital renal malformations that result in oligohydramnios

Answer 348

Areas of disrupted mesothelial cells in the visceral pleura that may contribute to the risk of pneumothorax

Answer 349

Air accumulates under the parietal pleura external to the lung parenchyma - causes direct compression of the lung Classically occurs at rest but may be precipitated by a maneuver that increases intra-thoracic pressure (Valsalva) or by lifting and straining.

Answer 350

It occurs when air leaks into the pleural space and is unable to drain Air will accumulate with each inspiratory effort and collect under "tension" = tension pneumo Medical emergency - it may ultimately result in decreased cardiac output and arrest

Answer 351

Light method Rhea method Collins Method Also: Measuring the distance to the cupola or apical dome of the lung (considered large if greater than 3 cm to the apex), distance to the lateral edge (considered large if >2 cm) or complete dehiscence

Answer 352

Volume (%) = 100 - [(average diameter lung)^3/(average diameter hemithorax)^3 x 100 ]

Answer 353

Average of inter pleural distances (cm) at 3 points on erect CXR 1. Apex 2. Midpoint upper half of lung 3. Midpoint lower half of lung Use nomogram to convert into volume

Answer 354

Size (%) = 4.2 + 4.7 [sum of inter pleural distances at apex, midpoint upper half of collapsed lung, and midpoint lower half of collapsed lung]

Answer 355

The presence of a visible rim of >2 cm between the lung margin and chest wall at the level of the hilum

Answer 356

No Adult pneumothorax guidelines recommend avoiding scuba diving unless a definitive surgical procedure, such as a bilateral pleurectomy, has been undertaken and normal lung function and chest CT have been confirmed postoperatively

Answer 357

There is a risk that if a pneumothorax occurs while the diver is under water, it will enlarge during the ascent in accordance with Boyle’s law, and the diver may develop a rapidly enlarg- ing pneumothorax—a potentially life-threatening situation.

Answer 358

No Patients with a closed pneumothorax should not fly owing to low cabin atmospheric pressure. There should be no increased risk of developing a recurrent pneumothorax with flying after a PSP; however, the pneumothorax must be entirely resolved, with radiologic confirmation The BTS air travel guidelines recommend that complete resolution of the pneumothorax be confirmed on CXR and that then a minimum 7 days should elapse prior to flying, with a longer delay if the pneumothorax was traumatic or if the patient has underlying lung disease

Answer 359

1. Exudative stage—simple parapneumonic effusion with low leukocyte count. 2. Fibrinopurulent stage—deposition of fibrin resulting in septations and loculations. An increase in leukocytes occurs and microorganisms invade the pleural space, resulting in purulent material filling the pleural cavity. A parapneumonic effusion that contains pus is defined as an empyema. 3. Organizational stage—fibroblasts enter the pleural cavity, forming tight fibrous membranes.

Answer 360

The process of pleural fluid accumulation is mediated by increased vascular permeability secondary to mesothelial cell cytokines including interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, and platelet activating factor. Initially the fluid accumulating in the pleural space is an exudate resulting from the inflammatory process involving the pleura in response to an underlying pneumonia. The pleura leaks proteins and fluid and eventually leukocytes. As the disease progresses, the number of leukocytes increases, and eventually the pleural cavity is infiltrated by organisms. When the fluid becomes purulent, it is called an empyema

Answer 361

As the disease progresses, there is increasing deposition of fibrinous material, which leads to septation and the formation of loculations. This fibrinous material can obstruct the free flow of fluid and block the draining lymphatic stomata, thus preventing spontaneous resolution of normal lymphatic draining and often requiring an intervention to drain the fluid

Answer 362

Fibroblasts penetrate the pleural cavity and can form a membrane called a peel. This peel is made of firm fibrous material that can impair lung function by “trapping” the lung and limiting recovery if not identified. Although lung trapping is often seen in adult patients, it rarely occurs in children with empyema

Answer 363

Empyema should be considered in children who do not respond to appropriate antibiotics within 48 hours, as evident by ongoing fevers, toxicity, and respiratory distress. In this scenario a CXR should be undertaken to assess for progression of the pneumonia or pleural fluid collection.

Answer 364

No The BTS and Australian guidelines for pleural infection in children do not recommend that all otherwise healthy children routinely undergo immunologic testing in the setting of a single empyema. However, the guidelines acknowledge that immune deficiency syndromes have been diagnosed in this way, and investigations should certainly be undertaken in the setting of a child with a history of repeated infections, unusual infections or a family history of immune deficiency. Guidelines recommend that if S. aureus or P. aeruginosa is identified as the causative organism, a sweat test to exclude cystic fibrosis should be arranged.

Answer 365

Inherited disorder characterized by defects of motile cilia → impaired ciliary motion → ineffective mucociliary clearance → rhinitis, sinusitis, otitis media, and bronchitis → bronchiectasis 50% have situs inversus totalis or other laterality defects (but 25% of patients with situs inversus have PCD) Associated with male infertility due to defective sperm tail structure Kartagener = clinical syndrome manifested by triad of situs inversus, chronic sinusitis and bronchiectasis

Answer 366

Large airways and contiguous structures (nares, sinuses, middle ear) are lined by ciliated, pseudostratified columnar epithelium Other epithelia that contain motile cilia are the ependyma of the brain and fallopian tubes + flagella of sperm are similar in core structure Mature resp ciliated cells have about 200 cilia with av. length of 6 um and diameter of 0.2 um

Answer 367

Each cilium contains 9 doublets of microtubules arranged in an outer circle around 2 Microtubules are anchored by a basal body in the apical cytoplasm of the cell ● Tubulin – main protein of microtubules ● Nexin - links the outer microtubular doublets ● Radial spokes – connects outer microtubular doublets with central tubules ● Dynein – attached to microtubules as inner and outer arms (thought to participate in provision of energy for microtubule sliding through ATPase activity)

Answer 368

Ciliary motion = 2 phases 1) stroke phase: sweeps forward – tips of cilia contact the overlying mucous to propel it forward 2) recovery phase: cilia bend backward and extend in to the starting position for the stroke phase – lose contact with mucous Beat frequency faster in the proximal airways than distal airways (12 beats/sec in the nose and trachea vs. 8 beats/sec in the bronchioles) and in kids than adults (13 beats/sec vs. 11.5 beats/sec) Mucociliary transport rates can be as rapid as 20-30 mm/min

Answer 369

1. Ultrastructural (Dynein arms – 80% of PCD patients, partial absence of inner dynein arms can be seen in normal subjects) 2. Functional

Answer 370

``` Nasal nitric oxide measurement Ciliary biopsy with electron microscopy PCD genetic testing panels Functional ciliary beat/waveform analysis with high speed videomicroscopy Immunofluorescence testing ```

Answer 371

1) Unexplained neonatal respiratory distress (at term birth) with lobar collapse and/or need for respiratory support with CPAP and/or oxygen for >24 hr 2) Any organ laterality defect - situs inversus totalis, situs ambiguous, or heterodoxy 3) Daily, year-round wet cough starting in first year of bronchiectasis on chest CT 4) Daily, year-round nasal congestion starting in first year of life or pan sinusitis on sinus CT

Answer 372

Newborn: tachypnea, cough, hypoxemia Children: chronic productive cough, recurrent/chronic resp infections, rhinitis/nasal congestion, sinusitis, chronic OM, bronchitis, pneumonia, clubbing Adults: male infertility due to impaired sperm motility, questionable increased female infertility/ectopic pregnancies Other potential issues: hydrocephalus (? defective ventricular ependymal cilia), defective leukocyte migration (? defective cytoplasmic microtubules) Situs inversus totalis occurs in 50% of PCD patients → due to dysfunctional embryonic nodal cilia → random thoracoabdominal laterality Heterotaxy (situs ambiguous) occurs in 6% → associated with CHD, abdominal situs inversus, polysplenia (left isomerism) and asplenia (right isomerism and Ivemark syndrome)

Answer 373

Frequent (>60%) - Hyperinflation - Bronchial wall thickening - Segmental or subsegmental atelectasis - Mucosal thickening of the paranasal sinuses Common (20-60%) - Situs inversus - Bronchiectasis - Opacification of paranasal sinuses 100% adults have bronchiectasis – mostly in middle lobe, lingual and lower lobes

Answer 374

H flu, Staph, Strep pneumo or viridans later Pseudomonas, mycobacterium avium and abscessus

Answer 375

Enhance mucus clearance: chest physio +/- nebs - NB: cough is an effective clearance mechanism in PCD patients - Hypertonic saline NOT pulmozyme - pulmozyme assoc w/ worse outcomes (one study) - Prevent resp infections: routine imm + pneumococcal and yearly flu, avoid smoke/pollutants - Treat bacterial superinfections: antibiotics, tympanostomy, sinus drainage - Lobectomy, Lung transplant - Prognosis: Bronchiectasis + some degree of pulmonary disability. Many w/ normal/near-normal lifespan

Answer 376

CXR q2-4 years CT consider at least once after 5-7 years Airway microbiology cultures 2-4 times/year Non-TB mycobacterial cultures q 2 years (and with unexplained decline) PFT testing 2-4 times/yr ABPA testing: IgE levels +/- evidence of aspergillum specificity at diagnosis, with new onset wheezing, unexplained clinical decline

Answer 377

Airway clearance: daily Nasal sinus lavage: daily Standard vaccinations: per local schedule Influenza vaccine: Annually

Answer 378

Results from Hemoglobin-S (HbS) which polymerizes in the deoxygenated state Polymerization -> Microvascular occlusion (any tissue) -> vaso-occlusion -> ischemia/infarction Hemolysis results in release of intracellular RBC arginase (Arginine is the substrate for NO synthase, therefore Arginase depletes arginine levels) → depletion of NO 2. Free Hgb binds to NO, further reducing NO bioavailability Decreased NO thought to lead to endothelial dysfxn → elevated TRJV (proxy for elevated pulmonary artery pressure)

Answer 379

1. Chronic Lung Disease -> PH 2. Acute Chest Syndrome (ACS) 3. Comorbid Asthma/SCD 4. Sleep disordered Breathing 5. Pulmonary Embolus - fat embolus, thromboembolic 6. Plastic bronchitis (has been described)

Answer 380

Most common: - Infection with encapsulated bacteria (S. pneumo, H. flu) - Pain crises - Acute chest crisis (ACS) - Cerebral infarcts - silent and overt

Answer 381

(Kendig) 1. Fever +/- Respiratory Symptoms 2. New radio-density on CXR 2nd most common reason for admission - More common in SCD-SS, and SCD-𝛃0 - 50% with SCD-SS have at least one ACS - Peak incidence 2-4 years - One episode at 3 year or earlier = greatest RF for future ACS Physical findings - Inspiratory crackle (75%) > Wheeze (~33%) - Leading cause of premature death in SCD - Difficult to distinguish from viral illness / asthma - Often no trigger found: ~50% of cases - Causes: Infection 30% > Pulmonary Infarction 16% > Fat Embolus 8% - Infection triggers: Viral, chlamydial, mycoplasma, bacteria, mixed.

Answer 382

Oxygen to maintain sats >92% Monitoring Antibiotics: typically cover S. pneumo (3rd gen ceph) & Atypicals (macrolide) as common in ACS Salbutamol trial May require blood transfusion, exchange transfusion Intubation and ECMO have been required for some NIV - acute improvement in RR, oxygen need, no difference in outcomes Steroids NOT generally recommended: shorter stays, but increased rebound pain + rehosp. Of note: Admission for VOC = RF for ACS During VOC admission: incentive spirometry REDUCES rate of ACS

Answer 383

1. Treatment of underlying asthma 2. Pre-operative blood transfusion 3. Chronic transfusion for recurrent ACS (typically short-term <12mo) 4. Maintenance of hydroxyurea 5. Incentive spirometry during VOC - supposed to use q2h when awake

Answer 384

Exact natural history remains unclear - Speculation: Normal → Obstructive → Restrictive - Typically Normal Early; Restrictive Late. But progression unclear. - Both obstructive and restrictive disease more common in SCD than general population - Chronic lung disease worst in SS-Disease - CLD worse with age - With age, restrictive disease > obstructive disease (mixed may also occur) - Postulated that ACS contributes to restrictive disease CT Findings in adulthood: - Lobar volume loss = associated with ↓ FEV1, FVC, TLC - Prominent central vessels - Reticular pattern, and ground glass opacification - Restrictive dz = 2° to fibrotic interstitial abnormalities

Answer 385

Rightward shift on oxy-hgb desat curve: ↓ affinity of HbS, & Incr 2,3-DPG 2° to hemolysis Dyshemoglobins incr: MthHb, COHgb2 Low PaO2 (IE due to V/Q mismatch, diffusion abnormality, etc.) Low daytime awake SpO2 common in SCD - Has been related to: ACS, older age, low HbF, OSA, asthma, Hgb-level - Note: HbS is abnormal, oximeters not calibrated to HbS - Also increased variability may occur, since SpO2 may be closer to steep part of curve - Potential effects of low sats: pHTN/↑TRV, ACS, VOC, stroke / silent infarct, cognitive dysfunction

Answer 386

Theoretically higher risk: lymphoid hyperplasia, airway narrowing from bone marrow hyperplasia

Answer 387

Positive methycholine found to be associated w/ IgE, high LDH (marker of hemolysis) Airway hyper-responsiveness NOT assoc with increased ACS prevalence Doctor diagnosed asthma in SCD associated with increased ACS, Pain crisis DocDx asthma independent risk factor for death Atopy (positive skin testing to an aeroallergen) occurs at a similar rate in SCD -However positive skin testing assoc w/ recurrent ACS, & atopic asthma in SCD = ↑ACS

Answer 388

Regular hematology follow-up Involve pulmonologist if asthma suspected, or ANY ACS -Preventative strategies to prevent morbidity/mortality Penicillin BID until 5 years Conjugated vaccines (+extended vaccines) for S. pneumo, H. flu Supplemental folic acid - maintain erythropoiesis Hydroxyurea - to increase HbF - decreases ACS / pain crisis ~50% Monitor adherence PFT and lung volumes annually starting at age 6 (Spiro with every visit if they have asthma) Lung volumes q5 years in children with no asthma or ACS episodes Bronchodilator challenge should be done in those with obstruction on PFT

Answer 389

1) Restrictive or obstructive lung pattern on PFTs 2) Airway hyperresponsiveness 3) Low oxygen saturation

Answer 390

1) Pulmonary vascular disease (decreased perfusion secondary to sickled cells) 2) Anemia (should be adjusted based on HgB level) 3) Pulmonary hypertension 4) Fibrosis/ILD

Answer 391

Also referred to as alveolar capillaritis, is characterized by neutrophilic infiltration of the alveolar septa (lung interstitium) -> necrosis of these structures, loss of capillary structural integrity and spilling of RBCs into the alveolar space and interstitium

Answer 392

``` The systemic vasculitides Anti-glomerular basement membrane (anti-GBM, Goodpasture’s) disease Rheumatic diseases Certain drugs Idiopathic pulmonary hemosiderosis, Idiopathic pulmonary capillaritis ``` Idiopathic pulmonary capillaritis, also known as pauci-immune pulmonary capillaritis, is characterized by the histopathologic findings of pulmonary capillaritis, but without clinical or serologic evidence of an associated systemic illness

Answer 393

Present with signs and symptoms of alveolar hemorrhage without renal or other systemic manifestation Diffuse alveolar opacities on imaging Low hemoglobin Hemosiderin-laden macrophages on BAL Normal kidney function Associated with lower hemoglobin and higher ESR (compared to IPH) Usually positive ANCA - if not, need biopsy

Answer 394

Subtype of group 1 (PAH) PVOD may represent a common aberrant response to an inciting event of endothelial injury that leads to widespread fibrosis of pulmonary venules Many patients with PVOD additionally have findings of capillary congestion and lymphadenopathy, but with a normal-sized left atrium and normal-sized major pulmonary veins The presence of venous congestion and lymphadenopathy with a normal-sized left atrium and normal-sized major pulmonary veins are features that may help distinguish PH due to PVOD from other causes of post-capillary PH, namely that due to left-sided heart disease These features are likely due to chronic pulmonary capillary hypertension, transudation of fluid into the interstitium, and enlargement of pulmonary lymphatic channels.

Answer 395

PVOD is a fibroproliferative disease primarily affecting the small pulmonary veins with relative sparing of the larger veins. The pathologic hallmark of PVOD is extensive and diffuse occlusion of the pulmonary veins due to smooth muscle hypertrophy and collagen matrix deposition (ie, fibrous tissue).

Answer 396

1. Iron deficiency Anemia 2. Hemoptysis 3. Diffuse infiltrates on imaging

Lung Disease (Miscellaneous) Flashcards

(423 cards)