APPROACH TOINTERSTITIAL LUNG DISEASE Dr Nahid Sherbini Pulmonary Fellow
OBJECTIVES• Review the spectrum of ILD or DPLD• Identify clues on presentation to make the diagnosis• Review common radiographic findings in ILD• Role of BAL,TBBX and OLB in the diagnosis of ILD• An algorithm to make the diagnosis
INTRODUCTION• (ILDs) are a heterogeneous group of disorders that are classified together because of similar clinical, radiographic, physiologic, or pathologic manifestations .
WHAT IS THE PULMONARY INTERSTITIUM?• between the epithelial and endothelial basement membrane• Expansion of the interstitial compartment by inflammation with or without fibrosis • Necrosis • Hyperplasia • Collapse of basement membrane • Inflammatory cells
• "interstitial" reflects the pathological abnormality begins in the interstitium extensive alteration of alveolar and airway architecture.
PATHOGENESIS The pathogenesis of ILDs is unknown. But more and more facts have shown that immune cells and their cytokines play an important role in the course of ILDs.
NOWADAYS THE MAJOR COURSES OF THE ILDSINCLUDING:• Intra-alveolar inflammation• Immune cells and their cytokines injure epithelial and endothelial cells• Intra-alveolar fibrosis/alveolar collapse
In the course of ILDs many cytokines involved in :including TGF- , IGF- , prostaglandin E2, platelet-derived growth factor, ects,.
CLASSIFICATION• Divided into-Associated with known causes and-Idiopathic. The treatment choices and prognosis vary among the differentcauses and types of ILD
DPLD Idiopathic Granulomatous DPLD of known Interstitial Lung Diseases Others Cause Pneumonias (Sarcoidosis) LAMDrugs Exposure CVD IPF IIP other than IPF Histiocytosis X Malignancy Respiratory Desquamative Hypersensitivity Bronchiolitis- Pneumoconiosis Interstitial Pneumonitis Interstitial Lung Pneumonia disease IPF: 47-64% Cryptogenic Acute Interstitial Organizing NSIP: 14 to 36% Toxic Inhalation Radiation Pneumonia Pneumonia RBILD/DIP: 10- 17% Lymphocytic Non Specific COP: 4-12% Interstitial Interstitial Pneumonia Pneumonia AIP: 2% LIP: 2%
INCIDENT CASES OF ILD Occupation 11% DILD Sarcoidosis 5% DAH 8% 4% CTD 9% Other 11% Pulmonary Fibrosis 52%(Incidence of IPF=26-31 per 100,000) Coultas AJRCCM ; 150:967
HISTORICAL CLASSIFICATION OF IIP UIP/IPF UIP UIP DIP RB- ILD 2002 DIP ATS/ERS NSIP UIP-BO DIP-RBILD LIP AIP AIP Giant cell IP Cellular NSIP Fibrotic 1970 1997 COP Liebow and Carington KatzensteinAdapted from Ryu JH, et al. Mayo Clin Proc. 1998;73:1085-1101. LIPAdapted from ATS/ERS. Am J Respir Crit Care Med. 2002;165:277-304.
HISTORY: SMOKING• All of the following DPLD are • In Goodpasture’s syndrome associated with smoking • 100% of smokers vs. 20% of except: nonsmokers experience a) IPF pulmonary hemorrhage b) RBILD • Individuals exposed to asbestos c) DIP who smoke are more likely to develop asbestosis. d) HP e) Histiocytosis X
PHYSICAL EXAMINATIONS• Bilateral basilar, crepitant velcro-like rale• wheezing, rhonchi and coarse rales are occasionally heard• with advanced disease, patients may have tachypnea and tachycardia• At last, pulmonary hypertention and cor pulmonale may be exist
• Anti-JO-1 ab even in the absence of clinical myositis, as ILD precedes the onset of myositis ~70% of patients with the anti- synthetase syndrome.
SERUM MARKERS SUGGESTIVE OF ILD• Surfactant protein A and B (SP-A, SP-B)• Monocyte chemoattractant protein-1 (MCP-1)• Kerbs von Lungren (KL)-6, a circulating, high-molecular weight glycoprotein expressed by type II pneumocytes.
• In one report, evaluated in a mixed population of patients with idiopathic ILD, collagen vascular disease-associated ILD, and controls with and without pulmonary disease KL-6 was associated with the highest sensitivity, specificity and diagnostic accuracy for the presence of ILD (94, 96, and 94 percent, respectively).• In the future, the KL-6 assay may help to identify and monitor ILD in patients with RA and other CTD.COMPARITIVE STUDYOF KL-6,SURFACTANT A ,B AJRCC 2002
CHEST RADIOGRAPHYIt is important method to diagnose the ILDs.
IMAGING -CXR• The correlation between the radiographic pattern and the stage of disease (clinical or histopathologic) is generally poor.• Honeycombing correlates a poor prognosis.• Review all previous chest films to assess the rate of change in disease activity.
CXR: LMITATIONS• CXR is normal: • in 10 to 15 % of symptomatic patients with proven infiltrative lung disease • 30% of those with bronchiectasis • ~ 60 % of patients with emphysema & HP• CXR has a sensitivity and a specificity of ~80% for detection of DPLD• CXR can provide a confident diagnosis in ~ 23 % of cases
A diffuse ground glass pattern early in the diseaseProgresses, nodules, linear(reticular) infiltrates, or a combination infiltrates become coarser and lung volume is losthoneycomb pattern
HRCT CLUES• What is the dominant HR-pattern: • Reticular • Nodular • High attenuation (ground-glass, consolidation) • Low attenuation (emphysema, cystic)• Where is it located (centrilobular, perilymphatic or random)• Is there an upper versus lower zone?• Central versus peripheral predominance• Are there additional findings (pleural involvement, lymphadenopathy, traction bronchiectasis)
CLASSIC IPF HRCT Basal and subpleural predominance Reticular opacities Traction Honeycombing bronchiectasisImage courtesy of W. Richard Webb, MD.
HRCT FINDINGS• Bilateral symmetric hilar adenopathy and upper lung zone reticular opacities sarcoidosis• Pleural plaques with linear calcification asbestosis.• Centrilobular nodules that spare the subpleural region hypersensitivity pneumonitis, sarcoidosis, Langerhans cell histiocytosis &respiratory, follicular, and cellular bronchiolitis.
HRCT FINDINGS• Irregular cysts associated with nodules in the upper and middle lung zones pulmonary Langerhans cell histiocytosis.• Subpleural and bibasilar reticular opacities associated with honeycomb changes and traction bronchiectasis are IPF Chronic hypersensitivity pneumonitis ILD-associated with RA.• In an asymptomatic patient, diffuse, calcified, nodular, interstitial opacities healed varicella-zoster pneumonia.
DIP: RADIOGRAPHICS• CXR: • Normal: 3-22% • Patchy GROUNG GLASS • lower zone predilection• HRCT: • Ground glass opacities • LL distribution (73 %) • peripheral distribution (59%)
PREDOMINANT HRCT PATTERN? Sjogren’s Syndrome “NSIP” WITH LIP
GALLIUM-67 LUNG SCANNING• Gallium-67 lung scanning is of limited value as a means of evaluating patients with ILD.
FDG-PET SCANNING• The role of (18)F-2-deoxy-2-fluoro-D-glucose (FDG) (PET) in the evaluation of ILD is unclear.• Positive FDG uptake can be seen inSarcoidosisPulmonary Langerhans cell histiocytosisLymphangitic carcinomatosisNot typically obtained in the evaluation of ILD.
CARDIAC EVALUATION• ECG pulmonary HTN, OR cardiac disease.• If heart failure BNP• ECHO• R HEART CATH WHEN NEEDED.
PFT• TOSeverityObstructive, restrictive, or mixed
PFT• A restrictive defect : (TLC), (FRC), (RV) ,(FVC) and (FEV1) but usually the changes are in proportion to the decreased lung volumes
AN INTERSTITIAL PATTERN ON CXR ACCOMPANIED BYOBSTRUCTIVE AIRFLOW SUGGESTIVE OF :1. Sarcoidosis2. Lymphangioleiomyomatosis3. Hypersensitivity pneumonitis4. Pulmonary Langerhans cell histiocytosis5. Tuberous sclerosis and pulmonary lymphangioleiomyomatosis6. Combined COPD and ILD7. Constrictive bronchiolitis
PFT• A reduction (DLCO) is a common, but nonspecific finding in ILD- , the severity of the DLCO reduction does not correlate well with disease prognosis, unless the DLCO is less than 35 % of predicted• Due to effacement of the alveolar capillary units but more importantly, to the extent of mismatching of V/Q of the alveoli.
MODERATE TO SEVERE REDUCTION OF DLCO IN THEPRESENCE OF NORMAL LUNG VOLUMES IN A PATIENTWITH ILD SUGGESTS ONE OF THE FOLLOWING:1. Combined emphysema and ILD2. Combined ILD and PVD3. PLCH4. LAM.
GAS EXCHANGE AT REST AND ON EXERTION• Resting ABG may be normal in early ILD ormay reveal hypoxemia (secondary to V/Q mismatch)CO2 retention is rare and usually a manifestation of end-stagedisease.
CARDIOPULMONARY EXERCISE TEST (CPET)• Desaturation• A failure to decrease dead space appropriately with exercise• Increase in RR with a lower than expected recruitment of TV physiologic abnormalities and the extent of disease.• CPET is not necessary for every patient with ILD.• a normal maximal CPET effectively excludes significant ILD .• Serial assessment of resting and exercise gas exchange is one of the methods used to follow ILD activity and responsiveness to treatment, especially in (IPF).
6MWT• 6MWT have correlated with prognosis in several studies of IPF .• Pulse oximetry desaturation to 88 during the 6MWT is associated with a median survival of 3.21 y compared with a median survival of 6.63 y in those who did not desaturate below 89%.
• The distance walked during the 6MWT is a reproducible measure and correlates with the maximal oxygen consumption (VO2max) obtained during a maximal exercise test .
ROLE OF BRONCHOALVEOLAR LAVAGE• The lavage fluid is sent for cell counts, cultures for mycobacterial, viral and fungal pathogens, and cytologic analysis.• Virtually all patients presenting with hemoptysis and radiographic ILD should undergo BAL to confirm an alveolar source of bleeding and identify any infectious etiologies.
• BAL is less likely to be helpful in patients with a radiographic pattern suggestive of IPF.• BAL does not have an established role in the assessment of ILD progression or response to therapy
LUNG BIOPSY• Obtained by flexible fiberoptic bronchoscopy, video-assisted thoracoscopic (VATS) biopsy, or open lung biopsy.• The histopathologic pattern found on the lung biopsy specimen is evaluated in combination with the clinical information to determine the diagnosis.
ROLE OF LUNG BIOPSY1. Atypical or progressive symptoms and signs (age less than 50 years, fever, weight loss, hemoptysis, signs of vasculitis)2. Atypical radiographic features3. Unexplained extrapulmonary manifestations4. Rapid clinical deterioration5. Sudden change in radiographic appearance.
VIDEO ASSISTED THORACIC SURGERY (VATS) • VATS is the preferred procedure for obtaining a lung biopsy High diagnostic accuracy Less morbidity and mortality than open lung biopsy BAL and TBBx limited to excluding other IPF mimickers • Ideal biopsy Two or more surgical wedge biopsies with areas of normal lung Samples should measure 3 5 cm in length and 2 3 cm in depth • Outpatient thoracoscopic lung biopsy can be a safe and effective procedure for patients with interstitial or focal lung disease Diagnosis obtained in 61/62 patients 72.5 % discharged home within 8 hours 22.5% discharged home within 23 hours ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664. Chang AC, et al. Ann Thorac Surg. 2002.74;1942-1946. Rena O, et al. Eur J Cardiothorac Surg. 1999;16:624-627.
PROBABILITY OF HISTOLOGIC DIAGNOSIS OF DIFFUSE DISEASES Transbronchial Surgical Biopsy Biopsy 1. Granulomatous diseases 2. Malignant tumors/lymphangitic 3. DAD (any cause) 4. Certain infections Often 5. Alveolar proteinosis 6. Eosinophilic pneumonia 7. Vasculitis 8. Amyloidosis 9. EG/HX/PLCH Sometimes 10. LAM 11. RB/RBILD/DIP 12. UIP/NSIP/LIP COP 13. Small airways disease Rare 14. PHT and PVOD Courtesy of Kevin O. Leslie, MD.
KEY POINTS:• Suspectinterstitial lung diseases with insidious dyspnea,even with minimal or no radiographic findings• A thorough history with exposures and systemic ROS is key• Firm diagnosis for IPF requires ruling out treatable causesand considering biopsy for atypical presentations