| Abstract|| |
Objective / Aim
The aim of our article is to present our early experience to evaluate High Resolution CT (HRCT) findings in Idiopathic Pulmonary Fibrosis (IPF) and to stress upon its clinical utility.
Materials & Methods
A prospective study of ten patients was done at and tertiary care government hospital. Study population comprises seven women and three men. Patients with chronic respiratory symptoms, chest radiograph showing typical reticular pattern or with clinical suspicion of IPF were selected. All patients underwent HRCT examination. Chest radiograph findings were compared with the HRCT findings in all patients. HRCT findings of our study were compared with the other studies.
From the study it was seen that IPF is most commonly manifested by the combination of HRCT findings, which includes peripheral (100%) and lower lobe predominance (80%) of the distribution of the lesions, evidences of intralobular septal thickening (100%), honeycombing (90%), traction bronchiectasis (90%) and parenchymal distortion (100%).
In conclusion, HRCT is accurate and superior in the confident diagnosis of IPF. HRCT findings in advance stage of IPF are characteristic. HRCT determines the disease activity and extent of IPF better than chest radiograph. When HRCT findings are characteristic in appropriate clinical settings, HRCT may obviate a need for open lung biopsy.
Keywords: Pulmonary fibrosis, HRCT, Interstitium
|How to cite this article:|
Raniga S, Sharma S, Arora A, Khalasi Y, Vora P A. Utility of high resolution computed tomography (HRCT) in diagnosis and management of idiopathic pulmonary fibrosis - a study of 10 cases". Indian J Radiol Imaging 2006;16:841-6
|How to cite this URL:|
Raniga S, Sharma S, Arora A, Khalasi Y, Vora P A. Utility of high resolution computed tomography (HRCT) in diagnosis and management of idiopathic pulmonary fibrosis - a study of 10 cases". Indian J Radiol Imaging [serial online] 2006 [cited 2020 Jul 6];16:841-6. Available from: http://www.ijri.org/text.asp?2006/16/4/841/32363
| Introduction|| |
Idiopathic Pulmonary Fibrosis (IPF) is defined as a specific form of chronic fibrosing interstitial pneumonia limited to the lung and associated with the histologic appearance of usual interstitial pneumonia (UIP) on surgical (thoracoscopic or open) lung biopsy ,. The etiology is unknown. IPF is a progressive, generally fatal disease, leading to volume loss and restrictive lung disease, decreased diffusing capacity, shortness of breath, and ultimately cor pulmonale.
The precise incidence and prevalence of IPF are not known. Previous prevalence estimates for IPF varied from 3 to 6 cases per 100,000 in the general population ,. Virtually all patients with IPF have an abnormal chest radiograph at the time of presentation . Indeed, basal reticular opacities are often visible on previous chest radiographs in retrospect for several years before the development of symptoms . In individuals with such asymptomatic abnormalities, investigation by physiologic evaluation or by high-resolution CT scanning (HRCT) could lead to earlier detection and treatment of IPF. Conversely, a normal chest radiograph cannot be used to exclude microscopic evidence of UIP on lung biopsy ,,. A surgical lung biopsy is necessary for a confident clinico-pathologic diagnosis except in cases with a typical clinical-radiological picture of IPF. Late in the course of the illness lung biopsy is least helpful.
The purpose of our study was to present our experience to evaluate of High Resolution CT (HRCT) findings in IPF & obviate its clinical utility.
| Materials & Methods|| |
A prospective study of ten patients with IPF was done. The selection criteria include the patients with chronic respiratory symptoms, chest radiographs suggestive of reticular pattern or spirometric evidence of restrictive lung disease. All patients underwent HRCT (TOMOSCAN-EG, PHILIPS, BEST, NETHERLANDS) examination. All images were obtained in suspended inspiration in supine position using 2mm collimation at 10mm interval from apex to the base of the lung at 120 kVp, 45 mA with 2sec exposure time and reconstructed with a bone algorithm. Additional prone images were obtained to differentiate dependent opacity and early interstitial changes.
The study included seven females and three males with IPF. The age group was between 42-75yrs. Mean age for IPF was 59yrs for both males and females. Pulmonary function test in these patients show evidence of restrictive pattern. None of our study population had history of exposure to drugs, collagen vascular disease, and radiation or fibrogenic drugs. The diagnosis was made on the basis of the criteria proposed by the American Thoracic Society (ATS) and The European Respiratory Society (ERS). The diagnosis of IPF can be made in the presence of four major and three minor criteria in the absence of open lung biopsy which is considered to be the Gold standard for the diagnosis of IPF . MAJOR CRITERIA: (1) Exclusion of known causes of infiltrative lung disease such as exposure to drugs, radiation, connective tissue disease. (2) Abnormal pulmonary function tests with evidence of restrictive pattern. (3) HRCT findings of bibasilar reticulation with minimal ground-glass opacity. (4) Transbronchial lung biopsy or bronchoalveolar lavage shows no evidence of another disease. MINOR CRITERIA: (1) Age older than 50 years. (2) Insidious onset of dyspnea on exertion. (3) Duration of illness of 3months or more. (4) Bibasilar inspiratory crackles.
The pattern, extent and distribution of HRCT findings were recorded, analyzed and compared with other studies.
| Results|| |
Our study included ten patients- seven men and three women with average age of 59 years. This is comparable to the studies of Lynch et al  in which the average age of presentation is 58.3 years.
Chest radiographic findings include bilateral reticular pattern in all ten patients and radiographic honeycombing in six patients (60%) (Fig.1). On chest radiograph, the disease was predominant in lower zones in eight patients and diffuses in two patients.
Following HRCT findings were seen- peripheral (100%) and lower lobe predominance (80%) of the distribution of the lesions, evidences of intralobular septal thickening (100%), honeycombing (90%), traction bronchiectasis (90%) and parenchymal distortion (100%) (Fig.2). These findings are comparable with the previous studies. In all patients honeycombing was bilateral; however, it was asymmetrical in three patients (Fig.3). Interlobular septal thickening was seen in only three patients (30%), relatively infrequent finding. Two patients (20%) show no zonal predominance and involve all the zones to an equal extent. Pleural thickening was seen in eight patients (80%). Extensive Ground glass opacity (GGO) was seen in 20% of the cases which is an infrequent finding as such. GGO should be considered to represent an active process only when there are no associated HRCT findings of fibrosis .
In our series, mediastinal lymphadenopathy was detected only in one patient (10%), however, routing 5mm sections in mediastinal window were not taken in our study- as this was not the focus of study and hence the detection of mediastinal lymphadenopathy may be different than the previous study.
| Discussion|| |
Many acute and chronic lung disorders with variable degrees of pulmonary inflammation and fibrosis are collectively referred to as interstitial lung diseases (ILDs) or diffuse parenchymal lung diseases . Idiopathic pulmonary fibrosis (or cryptogenic fibrosing alveolitis) (IPF or CFA) is one of several idiopathic interstitial pneumonias . IPF is the most common form of interstitial lung disease , of unknown cause and associated with a histological pattern of Usual Interstitial Pneumonia (UIP) . In the presence of a surgical biopsy showing a UIP pattern the diagnosis of IPF requires (1) exclusion of other known causes of interstitial lung disease including drug toxicities, environmental exposures, and collagen vascular diseases, (2) characteristic abnormalities on conventional chest radiographs or high-resolution computed tomography (HRCT) scans, and (3) abnormal pulmonary function studies showing restriction (reduced total lung capacity [TLC], or reduced vital capacity [VC] with a normal or increased FEV1/FVC ratio) and/or impaired gas exchange [increased P(A-a)O2 (alveolar-arterial pressure difference for O2), decreased PaO2 with rest or exercise, or decreased DLCO (diffusing capacity of the lung for CO)] .
Patients of IPF most commonly present between 40 and 70 years of age, typically with gradually progressive exertional dyspnoea, chronic cough (usually dry) and bibasilar inspiratory crackles ,,,,. Digital clubbing is seen in about two-thirds of patients with IPF ,,. Pulmonary function testing usually demonstrates a restrictive defect with reduced lung volumes and diffusing capacity ,,,. The routine laboratory evaluation of a patient suspected of having IPF is often not helpful except to "rule out" other causes of diffuse parenchymal lung disease .
A surgical lung biopsy is necessary for and confident clinico-pathologic diagnosis except in cases with a typical clinical-radiological picture of UIP/IPF . This is to say that a biopsy is not always necessary to make a clinical diagnosis. Pathology is least helpful when obtained late in the course of the illness or after commencement of treatment . Usual interstitial pneumonia (UIP) is the pathological abnormality essential to the diagnosis of IPF ,. The histological hallmark and chief diagnostic criterion is a heterogeneous appearance at low magnification with alternating areas of normal lung, interstitial inflammation, fibrosis, and honeycomb change ,,. These histological changes affect the peripheral subpleural parenchyma most severely . The earliest histological abnormality in IPF is alveolitis with increased cellularity of the alveolar walls ,. This inflammatory process can lead to progressive fibrosis. Alveolar wall inflammation and intra-alveolar macrophages in IPF indicate disease activity and are potentially reversible. Fibrosis and honeycombing are irreversible .
The mainstay of treatment for patients with IPF has been corticosteroid therapy, which is of unproved efficacy . The majority of patients diagnosed to have IPF, experience progression of the disease with or without therapy, resulting in cor- pulmonale and respiratory failure ,. In recent years, there has been increasing interest in anti-fibrotic therapy with agents such as colchicine and pirfenidone ,. A relationship between cigarette smoking and pulmonary fibrosis has been suspected for many years .
Virtually all patients with IPF have an abnormal chest radiograph at the time of presentation .The most common radiographic finding in IPF, described in approximately 80% of patients consists of bilateral irregular linear opacities causing a reticular pattern ,,. Although these opacities may be diffuse they involve predominantly the lower lung zones . Initially the reticular pattern is fine and granular and radiographically this is described as a ground-glass appearance ,. As fibrosis progresses, the reticular pattern becomes coarser, and there is progressive loss of lung volume. Honeycombing represents end-stage fibrosis. The plain radiographic appearance of IPF is nonspecific and misleading, being similar to that seen in many other interstitial lung diseases. Furthermore, it has been repeatedly demonstrated that the severity and extent of the disease assessed on the chest radiograph correlates poorly with the functional and clinical impairment ,. The clinical utility and optimal timing of follow-up chest radiographs are unclear. Radiographs are indicated if clinical deterioration occurs, to assess progression of disease, or to identify superimposed infection or malignancy .
HRCT scanning has changed the diagnostic evaluation of patients with IPF ,,. The predominant HRCT features of IPF include honeycombing and intralobular interstitial thickening; irregular interlobular septal thickening and ground glass opacity may also be present but are usually less conspicuous findings . The abnormalities are preferentially in the peripheral, subpleural region and lower lung zone and posterior predominance is usual ,. In our study, lower lobe predominance was seen in 80% & peripheral, subpleural predominance in 100% of the cases as compared to 81% & 91% by Lynch et al.
Another hallmark of IPF is patchy distribution. Areas of mild and severe fibrosis, inflammatory activity, and normal lung are often present in the same patient, in the same lung, and in the same lobe ,.
Reticular abnormality on HRCT correlates with fibrosis on histopathologic examination ,. Honeycombing on HRCT correlates with honeycombing on biopsy. When ground glass attenuation is associated with reticular lines, traction bronchiectasis, it usually indicates histologic fibrosis. Isolated ground glass attenuation may correlate with evidence of interstitial inflammation, airspace filling by macrophages, patchy fibrosis, alveolitis or a combination of these ,.
The intralobular septal thickening is the most common finding on HRCT in patients with IPF in 96% of cases  results in fine reticular pattern. Thickening of intralobular interstitium also results in the presence of irregular interfaces between the lung and pulmonary vessels, bronchi, and pleural surfaces . In areas of severe fibrosis, the segmental & subsegmental bronchi show traction bronchiectasis. In our study, intralobular septal thickening and traction bronchiectasis were seen in 100% and 90% of cases respectively, which is comparable to the previous study by lynch et al .
Honeycombing is another common finding associated with gross distortion of lung architecture, where individual lobules are no longer visible. Honeycomb cyst usually range from 2 to 20mm in diameter, appear to share walls on HRCT, occurs in subpleural lung and in several layers ,. Honeycombing occurs in 24-90% of patients who have IPF, and the frequency of this finding varies with the severity or stage of the disease ,. In our study it was seen in 90% of cases which is almost same as 88% as seen in Lynch et al study . Finding of honeycombing and fibrosis are most often bilaterally symmetrical ,, however it was asymmetrical in 30% of our study population.
Interlobular septal thickening is sometimes seen on HRCT, but is a less conspicuous finding than intralobular interstitial thickening or honeycombing. In patients with honeycombing septal thickening is only visible in less abnormal lung regions.
Ground-glass opacity (GGO) may be seen on HRCT and may indicate the presence of active inflammatory and potentially treatable disease. GGO should be considered to represent an active process only in the absence of associated HRCT findings of fibrosis . Findings of fibrosis in association with ground glass opacity, thus suggesting an irreversible process. Patients who have predominantly GGO on HRCT are more likely to respond to treatment than patients who predominantly have reticulation ,. IPF presenting with GGO as a predominant finding is distinctly uncommon ,. Presence of GGO as a predominant findings need further evaluation with lung biopsy. In our study GGO was seen in only 30% of the cases and in these patients it was not a predominant finding. This possibly represents our study population in advanced stage of disease.
Mediastinal lymphadenopathy usually less than 15 mm in short axis diameter & involving one or two nodal stations is seen in 46- 90% of patients of IPF . The likelihood of lymphadenopathy increases with the extent of parenchymal involvement and decreases in the presence of recent steroid treatment . This was in contrast to our study where only 10% of the cases revealed mediastinal lymphadenopathy. However, routing 5mm sections in mediastinal window were not taken in our study- as this was not the focus of study and hence the detection of mediastinal lymphadenopathy may be different than the previous study.
End stage lung disease was noted in most of our study population- with predominant finding of honeycombing (90%) and parenchymal distortion (100%). GGO was seen in 20% of cases; however it was seen in association with changes of honeycombing. GGO was not an isolated finding in any of our cases.
HRCT not only increases the level of diagnostic confidence but also helps in determining the disease activity and extent as well as avoiding unnecessary biopsy. The accuracy of a confident diagnosis of UIP made on HRCT by a trained observer appears to be about 90% .
In fact, most of the reported studies suggest that patients with IPF generally present late in the course of their disease . This point is particularly important since many of the features of IPF may be relevant only to the terminal phase of this disease process. Moreover, these findings indicate that efforts should be made to identify patients with IPF earlier in the course of their disease.
| Limitations of the Study|| |
The sample size is small but we have to consider the fact that the disease itself is rare with a prevalence of 3 to 6 cases per 100,000 in the general population ,.Case definition and population selection varies between studies; therefore, comparison of study populations is compromised. Most of our patients have extensive disease with gross changes on chest radiograph & CT as well. We have not taken into consideration the cases in early phase of disease. However, most of the reported studies suggest that patients with IPF generally present late in the course of their disease .
| Conclusion|| |
HRCT findings in advance stage of IPF are characteristic. HRCT determines the disease activity and extent of IPF better than x-ray chest. In presence of characteristic HRCT findings of IPF, invasive testing (lung biopsy) can be avoided.
| References|| |
|1.||Reynolds HY. Diagnostic and management strategies of diffuse interstitial lung disease. Chest 1998; 113:192-202. |
|2.||Coultas DB, Zumwalt RE, Black WC, Sobonya RE, The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med 1994; 150:967-972. |
|3.||King TE Jr,, Costabel U, Cordier JF. doPico GA, du Bois RM, Lynch D, Lynch JP III, Myers JL, Panos RJ, Raghu G, et al, Idiopathic pulmonary fibrosis: diagnosis and treatment. Am J Respir Crit Care Med 2000; 161: 646-664. |
|4.||Katzenstein AL, Myers JL, Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. American Journal of Respiratory Critical Care Medicine 1998; 157: 1301-1315. |
|5.||Nishimura K, Kitaichi M, Izumi T, Usual interstitial pneumonia: histologic correlation with high resolution CT. Radiology1992; 182: 337-342. |
|6.||Ryu JH, Colby TV, Hartman TE, Idiopathic pulmonary fibrosis: current concepts. Mayo Clin Proc 1998; 73:1085-1101. |
|7.||International Consensus Statement, Idiopathic pulmonary fibrosis: diagnosis and treatment. Am J Respir Crit Care Med 2000; 161:646-664. |
|8.||Turner-Warwick M, Burrows B, Johnson A, Cryptogenic fibrosing alveolitis: clinical features and their influence on survival. Thorax 1980; 35: 171-180 |
|9.||Johnston ID, Prescott RJ, Chalmers JC, Rudd RM, British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society. Thorax 1997; 52: 38-44. |
|10.||Ryu JH, Colby TV, Hartman TE, Vassallo Reference, Smoking-related interstitial lung diseases: a concise review. European Respiratory Journal2001; 17:122-132. |
|11.||Wells AU, Hansell DM, Rubens MB, Cailes JB, Black CM, and du Bois RM, Functional impairment in lone cryptogenic fibrosing alveolitis and fibrosing alveolitis associated with systemic sclerosis: a comparison. Am. J. Respir. Crit. Care Med. 1997; 155: 1657-1664. |
|12.||Travis WD, Matsui K, Moss JE, Ferrans VJ, Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns. Survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia. Am J Surg Pathol 2000; 24: 19-33. |
|13.||Muller NL, Colby TV, Idiopathic interstitial pneumonia: high resolution CT and histologic findings. Radiographics 1997; 17: 1016-1022. |
|14.||American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. American Thoracic Society. Am. J. Respir. Crit. Care Med. 2002; 165:277-304. |
|15.||Colby T, Carrington C. Interstitial lung disease. In: Thurlbeck WM, Churg AM, eds. Pathology of the lung. New York: Thieme, 1995: 589-737. |
|16.||Hansell DM, Wells AU. CT evaluation of fibrosing alveolitis- applications and insights. J Thorac Imaging 1996; 11: 231-249. |
|17.||Watters LC, King TE, Schwarz MI, et al, A clinical, radiolographic and physiologic scoring systemfor the longitudinal assessment of patients who have idiopathic pulmonary fibrosis. Am Rev Respir Dis 1986; 133: 97-103. |
|18.||Muller NL, Miller RR, Webb WR et al, Fibrosing alveolitis: CT pathologic correlation. Radiology 1986; 160: 585-588. |
|19.||Carrington CB, Gaensler EA, Coute RE. et al, Natural history & treated course of usual & desquamative interstitial pneumonia. Engl J Med 1978; 298:801-809. |
|20.||McLoud TC, Carrington CB, Gaensler EA, Diffuse infiltrative lung disease: and new scheme for description. Radiology 1983; 149:353-363. |
|21.||Muller NL, Guerry- Force ML, Staples CA, et al, Differential diagnosis of bronchiolitis obliterans with organizing pneumonia and usual interstitial pneumonia: clinical, functional & radiologic findings. Radiology 1987; 162: 151- 156. |
|22.||Staples CA, Muller NL, Vedal S, et al, Usual interstitial pneumonia: correlation of CT with clinical, functional, and radiologic findings. Radiology 1987; 162:377-381. |
|23.||Wells AU, Hansell DM, Rubens MB, et al, The predictive value of thin section computed tomography in fibrosing alveolitis. Am Rev Respir Dis 1993; 148: 1076-1082. |
|24.||Kazerooni EA, Martinez FJ, Flint A, Jamadar DA, Gross BH, Spizarny DL, Cascade PN, Whyte RI, Lynch JP, Toews G, Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring. Am J Roentgenol 1997; 169: 977-983. |
|25.||Leung AN, Miller RR, Muller NL, Parenchymal opacification in chronic infiltrative lung diseases: CT-pathologic correlation. Radiology 1993; 188: 209-214. |
|26.||Aquino SL, Webb WR, Zaloudek CJ, et al, Lung cysts associated with honeycombing: change in size on expiratory CT scans. AJR 1994; 162: 583- 584. |
|27.||Remy-Jardin M, Giraud F, Remy J. Importance of ground glass attenuation in chronic diffuse infiltrative lung disease: pathologic- CT correlation. Radiology 1993; 189: 693-698. |
|28.||Teriff BA, Kwan SY, Chan Yeung MM, et al. Fibrosing alveolitis: chest radiography & CT as predictors of clinical and functional impairment at follow up in 26 patients. Radiology 1992; 184:445-449. |
|29.||Franquet T, Gimenez A, Alegret X et al, Mediastinal lymphadenopathy in cryptogenic fibrosing alveolitis: the effect of steroid therapy on the prevalence of nodal enlargement. Clinical Radiology 1998; 53: 435-438. |
|30.||Iwai, K., Mori T, Yamada N, Yamaguchi M, and Hosoda Y, Idiopathic pulmonary fibrosis: epidemiologic approaches to occupational exposure. Am. J. Respir. Crit. Care Med1994. 150: 670-675. |
|31.||Scott, J., Johnston I, and Britton J, 1990. What causes cryptogenic fibrosing alveolitis? A case-control study of environmental exposure to dust. Br. Med. J. 301: 1015-1017. |
|32.||Johnston, I. D. A., Prescott RJ, Chalmers JC, Rudd RM, and for the Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society, British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Thorax 1997; 52: 38-44. |
|33.||Orens, JB., Kazerooni EA, Martinez FJ, Curtis JL, Gross BH, Flint A, and Lynch III JP, The sensitivity of high-resolution CT in detecting idiopathic pulmonary fibrosis proved by open lung biopsy: a prospective study. Chest 1995; 108: 109-115. |
|34.||Lynch DA, Newell JD, Logan PM, King TE Jr, Muller NL. Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis? AJR 1995; 165: 807 - 811. |
|35.||Mannino DM., Etzel RA, and Parrish RG, Pulmonary fibrosis deaths in the United States, 1979-1991: an analysis of multiple-cause mortality data. Am. J. Respir. Crit. Care Med. 1996; 153: 1548-1552. |
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[Table - 1]