Department of Pulmonary Medicine, Postgraduate Institute of Medical ... To study the clinical profile of patients with idiopathic pulmonary fibrosis (IPF) and.
ORIGINAL ARTICLE
Spectrum and Diagnosis of Idiopathic Pulmonary Fibrosis U. Maheshwari, D. Gupta, A.N. Aggarwal and S.K. Jindal Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
ABSTRACT Objective. To study the clinical profile of patients with idiopathic pulmonary fibrosis (IPF) and methods used for diagnosis. Methods. Prospective analysis of symptoms, signs, radiology and lung biopsy of patients freshly diagnosed to have IPF over a 16-month period. Results. During the study period, 76 patients (35 men) with a mean age of 50.6 ± 11.9 years were diagnosed to have IPF. Breathlessness (98.6%) and dry cough (92.1%) were the most common presenting symptoms. Transbronchial lung biopsy (TBLB) was performed in 38 (50%) patients. Histopathological examination revealed features consistent with IPF in 35 (92.1%) patients; two of the remaining three patients underwent open lung biopsy. Other patients were diagnosed based on clinical features and high resolution chest tomography (HRCT) findings. HRCT was performed in 69 (90.8%) patients; all had features suggestive of diffuse interstitial fibrosis. Conclusion. IPF is diagnosed more commonly now than in the past. Indian patients may be developing the disease a decade earlier than their counterparts in the West. TBLB and HRCT are useful in establishing diagnosis. IPF should be considered a distinct clinical entity rather than a diagnosis of exclusion. Key words : Fibrosing alveolitis, Age, Lung biopsy, High resolution computed tomography.
[Indian J Chest Dis Allied Sci 2004; 46 : 23-26]
INTRODUCTION The term diffuse parenchymal lung disease (DPLD), often used synonymously with interstitial lung disease (ILD), refers to diseases that cause inflammation of the pulmonary interstitium. About 200 disorders have been implicated in the causation of DPLD1. In about 30% patients, no definite aetiological agent can be identified; this subgroup had been conveniently designted as idiopathic pulmonary fibrosis (IPF). However, it is now well recognized that IPF constitutes a subgroup of DPLD
with distinctive clinical and histopathological features2. Since the time we first reported 61 patients with DPLD seen over a period of five years, of whom 46% were diagnosed to have IPF3 more than 20 years ago, the disorder is now diagnosed more frequently than in the past. We have recently prospectively evaluated the clinical profile and methods of diagnosis of IPF in patients with DPLD. This report includes 76 patients with IPF freshly diagnosed over a 16month period.
[Received : July 11, 2002; accepted after revision : March 12, 2003] Correspondence and reprints request : Dr S.K. Jindal, Professor and Head, Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012, India; Tele. : 91-0172-274758594, Extn 6821; Telefax : 91-0172-2745959; E-mail : .
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MATERIAL AND METHODS This study includes 76 patients with IPF selected from 158 patients diagnosed to have DPLD (based on clinical and radiological findings) at the Chest Clinic over a 16-month period, using an algorithm previously described by us4. Patients with a diagnosis of connective tissue related ILD, sarcoidosis, pneumoconiosis, or infection related DPLD were excluded from the study. A detailed history was recorded and physical examination performed in all patients at the time of initial presentation. Laboratory investigations included haemogram, liver and renal function tests, autoantibody screening for connective tissue diseases, electrocardiography, chest radiography and spirometry. Patients underwent fibreoptic bronchoscopy and transbronchial lung biopsy (TBLB) if they were physiologically fit (vital capacity>1 L, PaO2>60 mm Hg on room air). High resolution chest tomography (HRCT) was performed in patients not fit for, or not willing for, bronchoscopy. Both supine and prone films were obtained to characterize the interstitial pathology. In these patients, no further workup was performed if HRCT findings were consistent with IPF. In case the findings on HRCT were equivocal, an open lung biopsy was planned.
RESULTS There were 35 males and 41 females, their mean age was 50.6±11.9 years. Median age at diagnosis in men and women was 52 and 49 years respectively, and nine men (25.7%) and 11 women (26.8%) were aged more than 60 years. Seven men (20%) were smokers. Breathlessness (98.6%) and dry cough (92.1%) were the most common presenting symptoms, with a mean duration of 18.6±2.4 and 16.3 ± 2.0 months respectively. Extrapulmonary complaints included Raynaud’s phenomenon in one and joint pains in 10 (13.2%) patients. On clinical examination, clubbing was recorded in 42 (55.2%) patients. Fifteen (19.7%) patients had respiratory failure at presentation, of whom six (7.9%) had rapidly worsening dyspnoea
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progressing to acute respiratory failure. Three of these six patients required assisted ventilatory support before succumbing to their illness. Eight (10.5%) patients had corpulmonale at initial presentation; all responded favourably to decongestive measures. Chest radiographic findings included reticular shadows in 26 (32.8%), reticulonodular shadows in 45 (59.2%) and hilar enlargement in four (5.3%) patients. One patient had normal chest radiograph, but features strongly suggestive of IPF on HRCT chest. HRCT chest was performed in 69 (90.8%) patients. All patients had features suggestive of diffuse interstitial fibrosis. Other abnormalities noted on HRCT chest included honeycombing (n=61, 88.4%), ground glass haziness (n=16, 23.2%), parenchymal nodules (n=5, 7.2%) and insignificant mediastinal lymphadenopathy (n=4, 5.7%). Mild air trapping was observed in three patients. All three were smokers, and air trapping was considered to be related to smoking-associated small airway obstruction. Spirometry was performed in 64 (84.2%) patients, and was normal in 11 (17.2%) patients. One patient had an obstructive defect, while a restrictive defect was observed in the remaining 52 (81.2%) patients. Bronchoscopy and TBLB was performed in 38 (50%) patients. Histopathological examination revealed features consistent with IPF in 35 (92.1%) patients. In the other three patients, lung tissue was inadequate for opinion. Two of those patients underwent open lung biopsy. Usual interstitial pneumonia (UIP) was seen in one patient, while the other also had features of bronchiolitis obliterans in addition to features of IPF. One patient later underwent post-mortem lung biopsy, which revealed UIP.
DISCUSSION It is now well recognised that IPF is a distinct clinical entity rather than a diagnosis of exclusion. However, there is limited data on the presentation and diagnosis of these patients from India. In an earlier study from this
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Institute, data on patients with DPLD seen over a five year period were analysed3. Connective tissue disease related ILD accounted for 50.8% and IPF for 46% cases. In another study from Delhi5, IPF was seen in 28.6% of 133 patients with DPLD. There is an obvious increase in the number of patients of IPF diagnosed now than in the past. This could be attributed to factors such as increased awareness, greater availability of diagnostic procedures, increase in population, and possibly an actual increase in the incidence of IPF 6. In this background, we attempted to evaluate the clinical features and diagnostic studies carried out in these patients. In absolute terms, this report implies a greater than 10-fold increase in the number of patients with IPF seen annually by us, as compared to about 25 years ago. IPF is commonly seen in the middle-aged patients, and the incidence advances with increasing age7. As per Western reports, nearly two-thirds of patients are over 60 years of age at the time of diagnosis. In the present study, only 20 (26.3%) patients were aged above 60 years. Even in our earlier report, 89% patients were younger than 60 years3. Although there is a clear trend towards higher incidence of IPF with advancing age, the age at presentation is almost a decade earlier than that reported in Western studies7,8. Symptoms in patients of IPF include an insidious onset of dry cough and dyspnoea. In earlier reports, the incidence of cough has ranged from 26%-73% while that of dyspnoea ranged from 26% 100%,3,8,9. Clubbing may be seen in 25%-50% patients and ‘velcro’ crackles are present in more than 80% patients10,11. Acute respiratory failure at initial presentation was reported in 6% patients in an earlier study9. The overall prevalence of respiratoy signs and symptoms has almost been similar in our study. Lung biopsy has long remained the “gold standard” in establishing the diagnosis of IPF1. Although open lung biopsy was recommended earlier2,3, TBLB is now an easier approach with much less morbidity. At our Institute, TBLB is the investigation of choice for patients with DPLD, with a high diagnostic accuracy for
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establishing IPF, as seen from the results of the present study and earlier studies12. Open lung biopsy is undertaken only for patients in whom TBLB is inconclusive. The advent of HRCT as an imaging modality has obviated the need for a lung biopsy in many patients. Characteristic findings on HRCT scans are often sufficient to diagnose IPF. Trained observers can make a confident diagnosis of IPF in 90% patients in the presence of these radiological findings 13 . Although we earlier relied heavily on histopathological confirmation of disease, many more patients (especially those unable to undergo lung biopsy) are now being diagnosed based on HRCT scans. In the present study, typical radiographic findings were observed on HRCT in 88% patients. TBLB in the present study was performed only in half of the patients, it was avoided in others, either because of severe restriction on spirometry, or due to the presence of respiratory failure. In conclusion, the spectrum and clinical presentation of IPF is largely similar to that in the West, although Indian patients seem to develop the disease a decade earlier than their counterparts in the West. TBLB is useful in establishing diagnosis, although patients unable to withstand the procedure can be diagnosed based on the clinical features and HRCT findings. IPF should be considered a distinct clinical entity rather than a diagnosis of exclusion.
REFERENCES 1. British Thoracic Society. The diagnosis, assessment and treatment of diffuse parenchymal lung disease in adults : Introduction. Thorax 1999; 54 (Suppl 1) : S1-S14. 2. American Thoracic Society/European Respiratory Society International Multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002; 165 : 277-304. 3. Jindal SK, Malik SK, Deodhar SD, Sharma BK. Fibrosing alveolitis : A report of 61 cases seen over the past five years. Indian J Chest Dis Allied Sci 1979; 21 : 174-79.
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4. Jindal SK, Gupta D. Algorithm for diagnosing pulmonary fibrosis in tropical countries. Curr Opin Pulm Med 1998; 4 : 294-99. 5. Sharma SK, Pande JN, Guleria JS. Diffuse interestitial pulmonary fibrosis. Indian J Chest Dis Allied Sci 1984; 26 : 214-19. 6. Jindal SK, Gupta D. Incidence and recognition of interstitial pulmonary fibrosis in developing countries. Curr Opin Pulm Med 1997; 3 : 378-83. 7. Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med 1994; 150 : 967-72. 8. Louw SJ, Bateman ED, Benatar SR. Cryptogenic fibrosing alveolitis : Clinical spectrum and treatment. South Afr Med J 1984; 65 : 195-200. 9. Smith C, Feldman C, Levy H, Kallenbach JM, Zwi S. Cryptogenic fibrosing alveolitis : A study of an indigenous African population. Respiration 1990; 57 : 364-71.
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10. Johnston ID, Prescott RJ, Chalmers JC, Rudd RM and 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. 11. American Thoracic Society and the European Respiratory Society. Idiopathic pulmonary fibrosis : Diagnosis and treatment. International consensus statement. Am J Respir Crit Care Med 2000; 161 : 646-64. 12. Gupta D, Behera D, Joshi K, Jindal SK. Role of transbronchial lung biopsy in diagnosis of parenchymal lung diseases. J Assoc Physicians India 1997; 45 : 371-73. 13. Grenier P, Valeyre D, Cluzel P, Brauner MW, Lenoir S, Chastang C. Chronic diffuse interstitial lung disease : Diagnostic value of chest radiography and high resolution CT. Radiology 1991; 179 : 123-32.
