| What are interstitial lung diseases? | AKA diffuse parenchymal lung diseases, large number of acute and chronic conditions, among them is idiopathic interstitial pneumonias (chronic, acute or smoking related), granulomatous diseases.
It is important to differentiate between the causes of the disease in order to get the right prognosis and course of action. |
| What is IPF? | idiopathic pulmonary fibrosis, aka cryptogenic fibrosing alveolitis, chronic interstitial pneumonia associated with a pattern of interstitial pneumonia (not specific, could be seen in asbestosis/ occupational disease) |
| What is UIP? | Usual interstitial pneumonia, part of idiopathic interstitial pneumonias
It is the most common type (47-71%)
NSIP accounts for 13-48% of cases (non-specific) |
| What are the cardinal features of IPF? | progressive dyspnea and cough, bilateral interstitial infiltrates, restrictive physio, diffusion capacity defect in PFT.
(non-specific features)
dx of exclusion. |
| How is the epidemiology of IPF? | Rare, 3-41 /100,000 cases, but increasing (28% increase in a decade)
Much more in men, and elderly (after 6th decade), mortality more rapid in women smokers.
16,000 deaths in US annually |
| What are the etiologies of IPF? | Unknown cause, environment play a role, more current in smokers (increases risk by 3.6 times with familial cause)
Six exposures associated with it (smoking, farming, livestock, wood dust, metal dust and stone/sand
Chronic GERD may be a factor (fibrosis is complication of scleroderma involving esophageal dysmotility)
Genetics important (noted in 0.5-3.7% of pt) |
| What are the clinical features of IPF? | Initial: Dry cough and dyspnea, may become paroxysmal and debilitating and worsens with exercise.
PE: End-inspiratory rales often Velcro quality (85%)
Clubbing (25%), Extrapulmonary involvement not occurring (Suggests other disorders) |
| How is the clinical course of IPF? | Onset is indolent, inexorable progression over months to years.
variable course (stability for years may be, maybe rapid onset with respiratory failure over months, maybe gradual progression with acute exacerbations and abrupt fatal hypoxemia respiratory failure)
Spontaeous remission doesn't occur, survival mean 3-5 years, <15% survive past 10 years
Older age and severe impairments in HRCT or PFT suggest poor prognosis. |
| What are the last consequences of IPF? | Major cause of death is respiratory failure 70%.
Other causes include PE, lung cancer, cardio-vascular events (elderly)
Respiratory failure needs mechanical ventilator (may occur due to infection or acute exacerbation), but usually since high mortality we don't ventilate. |
| How is lung carcinoma in IPF? | Occurs in 4-13% of pt, risk greater in smokers (not only cigarette smokers), surgical resection may be curative in NSCLC, but high post op morbid and mortality. |
| How are acute exacerbations in IPF? | Accelerated course of the disease, terminal often, severe dyspnea, hypoxia, pulmonary infiltrate.
Resembles ARDS.
Factors causing it are unknown, viral infections, high O2 or drug reactions are etiologic factors.
usually fatal but favorable responses have been noted with IV pulse methylprednisone (limited cases) |
| What are labs done in IPF? | Non-specific labs.
ESR high, ANA and RF high (but less common 20%)
don't correlate with disease progression or therapy
CTD and hypersensitivity pneumonitis should be tested to rule them out |
| What are the image findings in IPF? | Interstitial infiltrates, Predilection for base and peripheral regions, all lung fields affected in later stages and lung volumes decrease
In HRCT: patchy basilar, peripheral and subpleural, honey comb (cystic radiolucencies - cardinal of UIP, absent in AIP and DIP), reticular opacities, ragged pleural surfaces, traction bronchiactasis, occasional ground glass opacities (not feature of UIP)
When HRCT are typical for UIP, we may not need a biopsy |
| What are the patterns, possible patterns and inconsistent patterns with UIP? | . |
| What is the prognostic quality of HRCT? | Ground-glass --> greater response to corticosteroids and survival than honeycombing.
Severe honeycombing ->mortaility within 2 years (80%)
FVC and DLCO are also predictors of mortality (more usefull) |
| How is the pathophysiology of IPF? | As all ILDs: reduced lung volumes, restrictive defect, normal or increased expiratory flow, impaired gas exchange and reduced DLCO (indirectly reflects vasculature (loss of alveolar walls of capillaries)
When emphysema occurs, lung volumes preserved and DLCO excessively reduced.
We have reduced compliance (esophageal balloon) , impaired oxygenation (worsens with exercise, hypoxemai at rest universal).
Cardiopulmonary stress test shows hypoxemia and widened A-a gradient (decreased O2 consumption with increased RR)
Severe derangements in PFTs or oxygentation -> poor prognosis
6-min walk test with oxymeter (Sat<88% mortality, O2 therapy needed, correlates with DLCO as well) |
| How is pulmonary arterial hypertension with IPF? | PAH and cor pulmonale are common in IPF, pathogenesis is complex and doesn't correlate with lung volumes.
artery remodeling, proangiogenic cytokines, ablation of vessels and vasoconstriction play a role
sPAH>50 associated with worse survival |
| How is the UIP microscopy? | Requires a SLB from 2-3 sites avoiding worse areas.
Temporal and geographic heterogeneity with fibroblastic loci and honeycomb.
Bilateral, patchy, basilar subpleural predilection lesions with low power magnification seen
Areas of active injury, inflammation, fibroblastic fibrosis and normal lung tissue are seen in same lobe.
Thickened alveolar wall (collagen, matrix, mononuclear infiltrates and fibroblasts)
Intra-alveolar macrophages, neutrophils and eosinophils (seen but not conspicous) |
| What is the use of BAL in UIP? | Broncho-alveolar lavage is useful to exclude etiologies that may mimic IPF (infection: pneumocystitis, mycobacteria, fungi, alveolar proteinosis)
No role in prognosis or staging or therapy,
Noted leukocytes, mast cells and alveolar macrophages |
| What is the treatment of UIP? | Lack of effective therapy, high-dose corticosteroids (0,5-1 mg/kg) with immunosupression
Panther IPF study showed harm in prednisolone + azathioprime (compared to a placebo mortailty increased with them)
NAC antioxidant (attenuates fibrosis in animals, no difference in FVC, rate, death or exacerbation noted)
Pirfenidone (reduces collagen synthesis, attenuates fibrosis - 45% redcuction of FVC and improved survival)
Nintedanib (thyrosine kinase inhibitor (VEGF and PDGF, reduced decline of FVC compared to placebo)
Lung transplant : best option, FVC<60%, DLCO<40%, oxygen depedency, 5 year survival 50% |
| What is NSIP? | Varying degrees of inflammation and fibrosis temporally uniform, scattered loci of pneumonia in 50%, accumulation of macrophages mimicking DIP 30%, key differentiating it from UIP is temporal uniformity
May be subacute, over weeks (not years like IPF)
Younger Pt, lymphocytosis seen, better prognosis than UIP, responsive to corticosteroids
5-year survival exceeds 70%, but still high mortality for fibrotic NSIP |
