1. Interstitial & Infiltrative Pulmonary Diseases
Prof.Dr. Abdul Hameed Al Qaseer

2. Diffuse Parenchymal Lung Diseases (DPLDs)
DPLD = Interstitial Lung Diseases ( ILDs)
ILDs are heterogeneous group of conditions asso-
ciated with diffuse thickening of alveolar wall with inflammatory cells & exudates ( e.g. ARDS) , granulomas( sarcoidosis) , alveolar hemorrhage
( Goodpasture syn.) , & /or fibrosis ( fibrosing alveolitis) .

4. Aetiology There are several causes of ILDs Some important causes are :
Sarcoidosis.
Idiopathic pul. Fibrosis( IPF)= cryptogenic fibrosing alveolitis (CFA).
Exposure to organic dust ( Farmer lung)
Exposure to inorganic dust e.g. asbestosis
ARDS.
Connective tissue diseases(CTD)e.g. SLE.
Some forms of pul. eosinophilia.
Rare disorders e.g. alveolar proteinosis .
Exposure to irradiation & drugs .

5. Relative frequency

7. Diagnosis of ILD( IPD) Establishing a diagnosis is important because :
There are prognostic implications.
To avoid inappropriate treatment .
Some DPLDs can expect to respond better .
A lung biopsy taken when the patient already establishing on empirical immunosupp. is associated with a higher mortality & morbidity & interpretation of the tissue obtained is more difficult.

8. Parasitic infestation ( pul. eosinophilia);
Initial Evaluation
1.History: Acute or chronic ; search for exposure to organic or inorganic dust ; smoking ; drugs ; skin rash ; joint pain or renal disease ; family history ………
Parasitic infestation ( pul. eosinophilia);
History of HIV infection ……..

9. Physical Signs
In the early cases there may be few ,if any physical signs. Latter on
tachypnea cyanosis , signs of pul, hypertension &/or cor pul.
Finger clubbing , restriction of lung expansion . End – inspiratory crackles +/- extrapulmonary finding .
Symptoms
Dyspnea is a common & prominent complaint .
Wheezing is uncommon ; chest pain is uncommon ; hemoptysis is rare.
Fatigue & weight loss are common in all ILD .

10. Investigations A. Laboratory:
Full blood counts
Calcium , LDH ( disease activity ), serum ACE , ESR ,
RF , ANF , serum precipitins , ANCA , …..
Other .
B. Chest imaging studies :
CXR: may shows reticular , nodular shadowing , honeycombing , or apical lesions.
HRCT: it is extremely valuable .
Gallium scanning .

12. CT of chest in IPF

14. C. Pulmonary function tests:
Spiromatry, lung volumes , gas transfer, exercise test .
Most of ILDs produce restrictive defect ( decrease TLC, RV,
VC ) & FVC1 / VC = normal or high .
Arterial blood gases may be measured especially in advanced diseases .
D. Bronchoscopy :
BAL , TBB , BB .
E. Lung biopsy : Open lung biopsy ,video-assisted thoracoscopy (VATS) ,mediostinoscopy +/- biopsy.
F. Other : Liver biopsy ,BMB …

15. Differential Diagnosis:
Infections : e.g. TB ,viral pneumonias , Mycoplasma,
parasitic , fungal .
2. Malignancy : e.g. leukemia /lymphoma ,metastasis,
Lymphatic carcinomatosis …….
3. Pulmonary edema .
4. Aspiration pneumonia

16. Sarcoidosis
It is a multisystem granulomatous disease ( most common in cold ); the lung affected in > 90%
The etiology of it remains uncertain.
The lesions are similar to TB (without caseation &tubercle bacilli not present).
Chronic beryllium poisoning produce a disease mimic to it
But this is now extremely uncertain .

17. Pathology:
The characteristic histological feature consist of non-casea-
ting epithelioid granulomas which usually resolve spontan-
eously .
All tissues may involved but most frequently affect ; med-
iastinal LN , superficial LN ,lungs ,liver ,spleen , skin , eyes
Parotid glands & phalangeal bones.

18. Clinical features
Acute sarcoidosis : with erythema nodosum ,peripheral arthritis , uveitis , bilateral hailer LAP, lethergy ,& occasionally fever.
Insidious onset :with cough , exertional SOB , or
one of the extrapulmonary manifestations.

19. Presentations of Sarcoidosis
Asymptomatic ( 30%) abnormal CXR , or LFT .
Respiratory & constitutional symptoms ( 20-30%).
Erythema nodosum & arthralgia ( 20-30%).
Ocular symptoms ( 5-10%) (sicca ….).
Skin sarcoid (including lupus pernio).
Superficial LAP (5%).
Other e.g. hypocalcaemia , DI, cranial nerve , cardiac ,
nephrocalcinosis.

21. Investigations
1.Tuberculin test negative in most cases( a strongly positive test may exclude sarcoidosis).
Biopsy from organ or LN or skin .
Transbronchial lung biopsy confirm the Dx in ~ 90%
( even in pat. with normal CXR)
Bronchoalveolar Lavage ( BAL) shows increased
lymphocytes .
4. Increase plasma levels of ACE ( for activity).
5. Lymphopenia , hypercalciuria , high ESR , hypercalceamia.

22. 6. CXR : also for staging :
Stage 1 : bilateral hilar enlargement .
Stage 2 : hilar shadow + pul. Opacity .
Stage 3 : diffuse lung shadow .
Stage 4 : pul. fibrosis .
7. Gallium ( positive in active )
8. PFT usually restrictive +/- impaired DLco.

23. Management Stage 1 & 2 usually resolves spontaneously .
Erythema nodosa + arthritis+ fever --- by NSAD
Short- term oral steroids is occasionally required in severe systemic feature , anterior uveitis , or hypercal.
Symptomatic stage 3 , eye , or other vital organs( e.g.
heart, brain ) need long-term treatment with corticosteroids ( mg /d reduces to mg /d)
or 20mg on alternate days for 6-24 months.
Methotrexate & hydroxychlorquine may be used as second line or steroid- sparing agents .
N.B. Patients with severe disease both methotrexate & azathioprine
used successfully.

24. Prognosis Features bsuggesting bad prognosis: > 40 years.
Afro- Caribbean .
Persistent symptoms > 6 months.
> 3 organs involvement.
Lupus pernio & stage 3 \ 4

25. Idiopathic Interstitial Pneumonias

26. Idiopathic pulmonary fibrosis (IPF)= CFA
IPF is the most common and important of idiopathic interstitial pneumonias ( > 85%) IPF has an incidence of ~ 6-10 / /year . More in smoker (2x) & in females.
The etiology remains unknown .
There is a strong association with cigarette smoking .

27. Clinical features of IPF
IPF is disease of elderly ( uncommon < 50 ).
It usually presented with slowly progressive SOB &non- productive cough .
Finger clubbing in 25-50% , central cyanosis in advanced .
O/E of the chest end( late ) inspiratory crackles .
Feature of cor pulmonale may be present ,& central cyanosis in advanced disease ..
Respiratory failure is the usual cause of death.
Heart failure & IHD are common , & accounting for ~ 1\3 of deaths.

28. Investigations of IPF RF & ANF in ~ 30-50%
ESR & LDH are high in most cases.
PFT usually shows restrictive patterns & DLco decrease.
PaO2 decrease
CXR lower zones bibasal shadows ---- honeycombing
HRCT is more sensitive & specific than CXR.
BAL & TBB to exclude other diseases.
Open lung biopsy if doubt exist .

29. Treatment of IPF
Glucocorticods are the main stay of thearpy ,but the success rate is low.
It is recommended for symptomatic ILD with IIP , eosinophilic pn. , sarcoidosis , CTD …………
A common starting dose is prednisolone , mg/Kg
for 4-12 weeks . The dose is tapered to 0.25 – 0.5 mg /Kg
for additional weeks .
If the patient's condition continues to decline while on steroid a second agent is often added e.g.
Cyclophosphomide & azathioprine 1-2 mg /Kg +/- steroid
An objective response usually requires at least 8-12 weeks to occur.

30. Treatment ( cont.) …….
If the above drugs have failed or could not tolerated, other
Agents , including …… methotrexate, colchicine , penicillamin . & cyclosporine have been tried .
2. If hypoxemia ( PaO2 < 55mmHg ) should be managed by
oxygen therapy .
Cor pulmonale & other complications should be treated
accordingly .
3. Lung transplantation may be considered in progressive disease not responding to all above measures .

31. New treatment
Treatment now targets the aberrant fibroblastic proliferation and tissue remodeling implicated in the pathogenesis.
Perfenidone , an antifibrotic agent.
Nintedanib , an intracellular inhibitor of tyrosine kinase.

32. Indications for transplantation in IPF
Dlco < 39%.
Decrement in FVC > 10% within 6 month.
Decreased in Spo2 < 88% during a 6-MWt.
Honeycombing on HRCT (fibrosis score > 2).

33. Respiratory involvements in CTD

34. Fibrosing alveolitis is a recognized complication of CTD .
The clinical features are usually similar to IPF .
1. Rheumatoid arthritis :
Pul. fibrosis is the most common .
Pleural effusion is also common , especially in men .
Caplan`s syndrome is the combination of rheumatoid
nodules & pneumoconiosis .
Bronchitis & bronchiectsis are both more common .
2. SLE :
Pul. fibrosis is relatively uncommon .
An acute alveolitis may be a life- threatening associated with diffused alveolar hemorrhage ( rare).
Pleuropulmonary involvement is more common .
“shrinking lung “ may be attributed to diaphragmatic
myopathy.

35. 3. Systemic sclerosis (SS) :
Most patients with SS eventually develop diffuse pul.
fibrosis (> 90%) .
“ hide bound chest “ due restrictive chest wall movement.