Diffuse cystic lung disease (DCLD)

Question 1

Types of cystic lung diseases

Answer 1

Question 2

Lymphangioleiomyomatosis (LAM) diagnostic test

Answer 2

A) Serum VEGF >800pg/mL

B) HRCT:
- thin-walled cysts, diffuse, round.
- the cysts may coalesce amd become atypically shaped
- others:
1) GGO (from smooth muscle proliferation/ pulm haemorrhage, lymphatic congestion)
2) septal thcikening
3) Chylothorax
4) Pericardial effusion
5) Thoracic duct dilatation
6) mediastinal nodes enlargement
7) cyctic lymphangioleiomyomas

C) Abdo & pelvic CT

D) Lung Bx if imaging/ VEGF not conclusive

E) PFT - usu obstructive, reduced DLCO

Question 3

Pulmonary Langerhans Cell Histiocytosis
- Epi
- Pathophysio
- Sx
- Ix
- Mx

Answer 3

Epi:
- Occurs in smoker >95%, and cannabis users
- Age 20-40y
- M=F

Pathophysio:
BRAF, MAP2KI and NRAS mutation –> activates MAPK pathway that recruits Langerhand cells to lung

Sx:
- Cough
- Spontaneous pneumothorax
- Fever, malaise, LOW, sweats
- Extrapulm: skin lesion, diabetes insipidus, osteolytic bone lesions
- Lung auscultation normal
- May develop pulm HTN

Ix:
1) HRCT:
- bilat, disseminated subcm nodules that may cavitate,
- with bizarrely shaped thick & thin-walled cysts,
- sparing the lung bases.
- The cysts will enlarge and become confluent resembling emphysema.
- Ground-glass attenuation suggests underlying smoking-related ILD.

2) PFT
- normal/ mildly impaired/ severe obstruction
- Low DLCO
- gas trapping

3) Lung Bx - gold standard

4) BAL - increase CD1a+ cells but low sens & spec

3) MRI brain - for pituitary gland Ax for diabetes insipidus

4) PET-CT - use for staging of the disease

Mx:
1) Smoking cessation
2) ICS & bronchodilators in reversible airway obstruction
3) OCS 0.5mg/kg/d, tapered 6-12m
(not much evidence but often used in rapidly declining PFT)
4) Cladribine - improves lung function & cysts size but SE are myelo & immunosupp
5) LTOT
6) Lung transplant

Question 4

Birt-Hogg-Dubé Syndrome (BHD)
- Epi
- Pathophysio
- Sx
- Ix
- Mx

Answer 4

Epi:
- autosomal dominant
- Tumour suppressor gene FLCN mutation that encodes protein folliculin
- any sex, any age (usu 30-40s)

Pathophysio:

Sx:
- recurrent spontenous pneumothorax (more common in asian than caucasian)
- cutenous fibrofolliculomas (more common in caucasion than asian)
- Renal tumours (up to 30%, can be recurrent & multiple)
- DOES NOT lead to loss of lung function or chronic resp problem

Ix:
1) Genetic test for FLCN gene
2) Skin HPE
3) HRCT: multiple elliptical pulmonary cysts, mainly in basal, subpleural, paramediastinal region
4) PFT - in multiple cysts & abnormal baseline PFT

Mx:
1) Pleurodesis for pneumothorax
2) Renal MRI to screen for renal tumour
3) Screen other family members with the genetic test
4) MDT - pulmonologist, geneticist, renal physician, CTC

Question 5

How to Dx LAM?

Answer 5

Compatible lung cysts on CT scan + (one of these):
1) tuberous sclerosis complexc (TSC)
2) VEGF-D ≥800
3) renal angiomyolipoma
4) Lymphandioleiomyoma
5) Chylous effusion

Lung Bx only if inconclusive from above

Question 6

Types of LAM

Answer 6

1) TSC-LAM
- Pt with underlying tuberous sclerosis complex (geneticly proven with TSC1 or TSC2 gene mutation) –> involves multisystem:
2) sporadic LAM
- has somatic mutation of TTSC2 gene

Question 7

What is the Rx for LAM?

Answer 7

1) mTORC1 inhibitor (Sirolimus)
- benefits: reduces loss of lung function/ chylous accumulation/angiomyolipoma growth
- indication:
a) FEV1 ≤70%
b) chylous
c) decline lung function ≥90mls/year
d) abnorm DLCO
e) air trapping, hyperinflation
f) hypoxic
- dose: 2mg per day thenm titrated to trough 5-15ng/ml
- SE: N,D, acne, peripheral oedema, hyperchol

2) Pleurodesis for pneumothorax (at initial episode, no need to wait for recurrence)
- future lung transplant is not contraindicated

3) Lung transplant
- indicated if FEV1 ≤30%, hypoxemia, NYHA 4, progressive lung function decline

4) Vacc - avoid live vax

5) LTOT - if hypoxic

6) Pulm rehab

7) Discourage from pregnancy - preg accelerates progression & increase risk of pneumothorax.
- Sirolimus needs to be wh during preg

Question 8

What is the epi of LAM?

Answer 8

Sporadic LAM is restricted to women
TSC-LAM can occur in male (but usu ASx)

Question 9

What are the Sxs of LAM?

Answer 9

Spontaneous pneumothorax
Chylothorax (20%)
Chylous ascites (5%)
Haemoptysis
Abdo pain (from angiomyolipoma rupture –> fatal)

Question 10

Lymphoid Interstitial Pneumonia (LIP)
- Epi
- Pathophysio
- Sx
- Ix
- Mx
- Complication

Resource: Uptodate

Answer 10

= infiltration of the interstitium and alveolar spaces of the lung by lymphocytes, plasma cells, and other lymphoreticular elements

Pathophysio:
- unknown
- assoc with autoimmune diseases (eg, Sjögren’s disease, systemic lupus erythematosus), and
HIV infection (? assoc with viral infectious)

Sx:
cough, dyspnea, and less commonly, weight loss and fever. Lung examination reveals crackles

Ix:
1) HRCT:
- ground-glass attenuation, centrilobular nodules (single or multiple) or masses, mixed ground glass-consolidative opacities, and septal thickening,
- lung cysts smaller number with lower zone predominance

2) Lung Bx - large sample

Mx:
1) ASx: not initiating treatment –> arrange f/up to Ax Sx functional and radiological progress.

2) Symptomatic = have physiologic impairment, progressive disease: oral prednisone 0.25 to 0.5 mg/kg given once a day (based upon the patient’s ideal body weight but not exceeding 60 mg/day), for 6 to 12 months.

3) If not responding to steroid, add on azathioprine/ cyclophosphamide/ cyclosporine/ rituximab

4) PCP prophylaxis in high dose steroid, also for HIV

5) Rx to prevent steorid complications

6) Antiretroviral therapy (ART) - initiate ART first before steroid.

Complication:
Malignant transformation of LIP to lymphoma may infrequently occur years after the initial diagnosis. Lymphomas arising from LIP lesions are associated with prolonged survival, as they are well differentiated and slow growing