Teaching clinic (Respiratory): Interstitial lung diseases Flashcards
What is interstitial lung disease?
Umbrella entity covering a heterogenous spectrum of lung diseases involving the interstitium/parenchyma of the lungs
* Inflammation and/or fibrotic processes taht involves the lung parenchyma
* A result of certain insults/injury to the lungs, and dysfunctional healing process
* Distribution: diffuse (more common, bilateral, multilobar), focal (occasionally)
What is the basic structure of a lung lobule?
Secondary lobules with lobule
Interlobular and intralobular septal thickening ddx?
- ILD
- Pulmonary congestion
- Lymphangitis carcinomatosis
What are the classes of interstitial lung disease that should be known?
IDP, COP, autoimmune ILD, drug associated ILD
What is the workup for patients with suspected ILD?
- Comprehensive history, physical examination
- Imaging: CXR, High resolution computed tomography (HRCT)
Functional assessment - Full lung function test including diffusion capacity
- 6-minute walking distance
- Arterial blood gas
Clues on possible etiologies from blood tests - Eosinophils,
- Muscle enzymes, Autoimmune markers
±Histology: bronchoscopy, CT-guided biopsy, video assisted thoracoscopy lung biopsy
Mr. Ng, 60
Presented with persistent cough, scanty mucoid sputum for 8 months
Progressive SOB on exertion
Weight loss of 5 pounds in three months
No other symptoms
PH: gall stone disease with cholecystectomy, non-obstructive left renal stone. ?COPD given Relvar Ellipta by private specialist
Non smoker, social drinker, hair stylist for 30 years
Reticulonodular shadow and right lower lobe
Describe the full lung test
Purpose of technician remarking that non smoker
what is the ddx?
FEV1/FEVC is normal: in restrictive lung disease it can be preserved till late stage where it wil be >80%.
In obstructive lung disease FEV1/FVC <70%
If just smoked before doing lung function test –> will effect the DLCO by decreasing the diffusing capacity due to carbon monoxide
ddx: ILD, bronchiectasis
Patient with interstitial lung disease what tests done?
- CBP, LRFT, Creatine kinase NAD
Immune markers - ANA 1/160
- RF, anti-dsDNA undetectable
- Anti-extractable nuclear antigen, anti-Jo1 negative
- Complement 3/4 normal
- C-reactive protein <0.35 mg/l
- Hepatitis B serology negative (done early if in the future requires immunosuppression or corticosteroid as treatment)
Define idiopathic pulmonary fibrosis
Idiopathic: no secondary causes identified
Pulmonary fibrosis that fulfilled specific radiological and/or histology pattern called usual interstitial pneumonitis (UIP)
What is the epidemiology of idiopathic pulmonary fibrosis?
What is the presentation?
What is the PE?
What needs to be excluded?
What is the HRCT features of usual interstitial pneumonitis (UIP)
- Honeycombing in subpleural and basal distribution
- With or without traction bronchiectasis
What are the histological features of usual interstitial pneumonitis?
- Established fibrosis with honeycomb changes, subpleural and paraseptal prominance
- Prominent fibroblast foci with comparatively mild interstitial inflammation
- Both temporal and regional heterogeneity
- Absence of other factors e.g. granuloma
What is further workup and monitoring for patients with idiopathic pulmonary fibrosis?
Quantify functional impairment
* Full lung function test
* 6-minute walking distance
* Oxygen saturation on room air, at rest and on exertion. Arterial blood gas
What is the disease course and prognosis of IPF?
What is the Mx of idiopathic pulmonary fibrosis?
predisposed individuals (short telomere/telomere mutations, mutations in innate immune genes such as MUC5b and TOLLIP), that lead to aberrant response to insults with excessive fibrosis
Mr. Chan, 68
Presented with mild dry cough for 2 months
No fever, dyspnea, appetite change or weight loss
Past history:
Aortic stenosis with AVR done in 1993, on warfarin
Sick sinus syndrome with tachy-bradycardia syndrome and dual chamber pacemaker implanted in 2019, frequent pAF with high ventricular rate, put on Amiodarone 200mg daily since December 2018
Ex-smoker, quitted 30 years, about 10 pack years
Retired teacher of primary school
PE: Temp 36.5 C, SaO2 98% RA. No clubbing. General examination was unremarkable.
Chest: scanty fine crepitation over R lung base
Comment on the CXR
- Pacemaker
- Two wire pacemaker: RA and RV
- Metallic aortic valve replacement
- Sternotomy stitches
- Scoliosis
- Bilateral lung infiltrates over lower zone
Complete blood picture
White cell count 6.7 x 10^9 /L (N: 4-11 x 10^9/L)
Hemoglobin and platelet normal
Liver and renal function within normal limit
C reactive protein 0.49 mg/dl (N <0.76)
Sputum: commensals, AFB smear –ve
What further Ix would you do?
Multilobular patchy infiltrates
Ground glass opacity (lighter color)
What ddx possible?
Infection
* Bronchopneumonia
* Septic emboli
* Aspiration pneumonia
Interstitial pneumonitis
* Any obvious precipitating factor
Interpret this lung function test
Reduced FEV1, FVC
Reduced TLC, VC
Reduced DLCO
FEV1/FVC <0.8 = restrictive lung disease
Drugs that are associated with interstitial pneumonitis
Mr. Chan, 68
Presented with mild dry cough for 2 months
No fever, dyspnea, appetite change or weight loss
Past history:
Aortic stenosis with AVR done in 1993, on warfarin
Sick sinus syndrome with tachy-bradycardia syndrome and dual chamber pacemaker implanted in 2019, frequent pAF with high ventricular rate, put on Amiodarone 200mg daily since December 2019
Ex-smoker, quitted 30 years, about 10 pack years
Retired teacher of primary school
PE: Temp 36.5 C, SaO2 98% RA. No clubbing. General examination was unremarkable.
Chest: scanty fine crepitation over R lung base
HRCT: patchy infiltrate with GGO
Lung function test: restrictive lung disease pattern
dx?
Radiological features?
Amiodarone induced interstitial pneumonitis
Radiology
* Non specific: can lead to many patterns of interstitial pneumonitis (e.g. focal or diffuse, ground glass/consolidation, or reticulo-nodular, fibrosis)
* Associated features: high attenutation in lung/liver/spleen related to deposition of iodine
Treatment for drug induced interstitial pneumonitis?
Withraw the culprit drug. Half life up to 3 months
Steroid may be considered for more severe disease
Mr. Kwong, 62
March 2020, presented with cough and mild breathlessness for 2 days
His wife and daughter were confirmed SARS-CoV2 infection
PMH: hypertension on amlodipine, hyperlipidemia on diet control, gout
Non-smoker, lives with wife, retired primary school teacher
- Admitted to isolation facility
- Temp 37.4 C, SaO2 96% RA, BP 120/80 mmHg, PR 100/min
- RR 18/min
- NP swab RT PCR SARS-CoV-2: positive; cycle threshold value (CTV) 14
- CXR was performed on day one
Worsened hypoxemic respiratory failure, intubated and mechanically ventilated on day 16
Three more doses of interferon beta-1b, after completion of 14-day antiviral regimen
Condition improved slightly, extubated to high flow oxygen therapy (FiO2 60%) on day 23
However, persistent hypoxemia requiring FiO2 50%
No fever,
CXR still showed extensive alveolar shadowing bilaterally
What were the possible causes of persistent hypoxemia?
- Refractory SARS-CoV2 pneumonia
- Pulmonary embolism
- Organizing pneumonia, perpetuating inflammation in lung parenchyma related to immune dysregulation
- Acute coronary syndrome with pulmonary edema
- Severe septicaemia with acute lung injury
Post covid
Describe HRCT
What is Mx?
Ground glass
Mid thorax –>Traction bronchiectiasis: late stage fibrosis (scarring pulls the airways open causing dilated airways) –> late
Reticular shadowing
if early = inflammation predominant for organizing pneumonia
Organizing pneumonia, post covid 19 –> dexamethasone 6mg daily iv proved to be effective.
What is organizing pneumonia?
What are possible HRCT patterns?
Defined pathologically by the presence of granulation tissue in distal airspace (alveolitis, bronchiolitis obliterans) progressing from fibrin exudates to loose collagen and fibroblasts
One type of inflammatory response to lung injury
* Idiopathic (cryptogenic organizing pneumonia, COP)
* Secondary
Possible HRCT patterns
* Typical: multiple patchy alveolar opacities with a peripheral and bilateral distribution (most typical)
* Less common: diffuse bilateral infiltration associated with interstitial opacities and small superimposed alveolar opacities
* Uncommon: solitary focal lesion
symptoms of cryptogenic organizing pneumonia (COP)?
Associated with what illness before?
- The onset of symptoms can be acute or subacute with fever, non-productive cough, malaise, anorexia, and weight loss
- Occasionally preceded by viral like illness
What are secondary causes of organizing pneumonia?
- Consequent to infectious pneumonia: despite elimination of the infectious organism by antibiotics, the inflammatory reaction remains active with organization of the intra-alveolar fibrinous exudate
- Drug related
- Connective tissue disorders
- Post-irradiation
Describe HRCT
Typical pattern: patchy consolidation in organizing pneumonia
This is RT pneumonitis: linear, well demarcated due to RT field
Describe HRCT
Organizing pneumonia
Less common pattern: diffuse interstitial infiltration and alveolar opacities
Describe HRCT
Organizing pneumonia
Uncommon pattern: solitary focal lesion
Other Ix in cryptogenic organizing pneumonia
- Restrictive defect on lung function test
- Elevated inflammatory markers on blood tests
Treatment of cryptogenic organizing pneumonia?
- Observe for mild case
- Corticosteroids (standard), 0.75-1mg/kg/day and adjust
- Most patients respond to steroids, with stabilization and improvement seen within days, and radiological resolution within weeks- months
Madam Dat, 48
Presented with exertional dyspnea and dry cough for 6 months
Also discoloration of fingers last winter
non-smoker, non-drinker, housewife, lives with husband and son
Told to have certain lung disease back in India in 2019
no joint pain
weight loss: 9kg in 2 years, appetite preserved
no photosensitivity
hair loss+
no oral ulcer
heart-burn for a few months
no swallowing problem
no dry eye, no dry mouth
P/E:
mild periungal erythema
no active arthritis
mild sclerodactyly
no muscle weakness
mild fine crepitation over left lung base
What Ix to do?
Ix:
ANA 1/320
anti-Scl70 positive
HRCT thorax done in India of Feb 2015: compatible with non-specific interstitial pneumonitis (NSIP)
Lung function test was arranged
Echo: trivial MR, TR, RVSP 30mmHg
Describe the lung function test and dx?
FEV1/FVC: high (93% more than 80%) —> restrictive lung disease
FEV1 and FVC reduced
DLCO is reduced (46%)
Parenchymal cause (reduced lung capacity and lung diffusion)
History of scleroderma —> NSIP
Systemic sclerosis 2 common forms of pulmonary involvement
Fibroblast dysfunction with resultant excessive collagen production and fibrosis
interstitial lung disease
Endothelial dysfunction resulting in a small-vessel vasculopathy
pulmonary arterial hypertension
Accounting for 60% of death of scleroderma patients
What is the ddx of chest symptoms in patients with scleroderma?
What is the interstitial lung disease in scleroderma?
What is the treatment of systemic sclerosis-ILD?
- Corticosteroids: unproven efficacy
- Cyclophosphamide: small gain in FVC, improvement in dyspnea and skin thickness in Scleroderma lung study 1 (SLS 1)
- Mycophenolate mofetil
- Nintedanib (anti-fibrotic agent): slows FVC decline
- Biologics: tocilizumab (anti IL6), rituximab
- Manage associated disease esp GERD and aspiration
