ILD2

Interstitial & Infiltrative Pulmonary Diseases

Prof.Dr. Abdul Hameed Al Qaseer

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) .

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 .

Relative frequency

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.

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 ……..


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 .

InvestigationsA. 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 .

CT of chest in IPF

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 …

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

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 .

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.

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.

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.

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.

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.

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 ( 20- 30 mg /d reduces to 7.5-10 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.

Prognosis

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

Idiopathic Interstitial Pneumonias

Idiopathic pulmonary fibrosis (IPF)= CFA
IPF is the most common and important of idiopathic interstitial pneumonias ( > 85%). IPF has an incidence of ~ 6-10 /100.000 /year . More in smoker (2x) & in females. The etiology remains unknown . There is a strong association with cigarette smoking .

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.

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 .

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 ,0.5-1.0 mg/Kg for 4-12 weeks . The dose is tapered to 0.25 – 0.5 mg /Kg for additional 4-12 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.

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 .

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.

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).



Respiratory involvements in CTD

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.

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