Pulmonary Fibrosis - Etiology & Diagnosis

10/03/01 (Parikh)

Question: What are the etiologies and diagnostic parameters for idiopathic pulmonary fibrosis?

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 21091585 / PubMed Identifier: 11177318

Authors: Selman M. King TE. Pardo A. American Thoracic Society. European Respiratory Society. American College of Chest Physicians.

Institution: Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, CP 14080, Mexico DF, Mexico. mselman@conacyt.mx

Abstract: Idiopathic pulmonary fibrosis is a progressive and usually fatal lung disease characterized by fibroblast proliferation and extracellular matrix remodeling, which result in irreversible distortion of the lung's architecture. Although the pathogenetic mechanisms remain to be determined, the prevailing hypothesis holds that fibrosis is preceded and provoked by a chronic inflammatory process that injures the lung and modulates lung fibrogenesis, leading to the end-stage fibrotic scar. However, there is little evidence that inflammation is prominent in early disease, and it is unclear whether inflammation is relevant to the development of the fibrotic process. Evidence suggests that inflammation does not play a pivotal role. Inflammation is not a prominent histopathologic finding, and epithelial injury in the absence of ongoing inflammation is sufficient to stimulate the development of fibrosis. In addition, the inflammatory response to a lung fibrogenic insult is not necessarily related to the fibrotic response. Clinical measurements of inflammation fail to correlate with stage or outcome, and potent anti-inflammatory therapy does not improve outcome. This review presents a growing body of evidence suggesting that idiopathic pulmonary fibrosis involves abnormal wound healing in response to multiple, microscopic sites of ongoing alveolar epithelial injury and activation associated with the formation of patchy fibroblast-myofibroblast foci, which evolve to fibrosis. Progress in understanding the fibrogenic mechanisms in the lung is likely to yield more effective therapies. [References: 193]

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 20421585 / PubMed Identifier: 10968375

Authors: Baumgartner KB. Samet JM. Coultas DB. Stidley CA. Hunt WC. Colby TV. Waldron JA.

Institution: Epidemiology and Cancer Control Program, University of New Mexico Health Sciences Center, Albuquerque, USA.

Abstract: Occupational exposures were investigated in a multicenter case-control study of clinically and histologically diagnosed idiopathic pulmonary fibrosis (IPF), a chronic diffuse interstitial lung disease of unknown etiology. Results are based on 248 cases, aged 20-75 years, diagnosed at 16 referral centers between January 1989 and July 1993. There were 491 controls ascertained by random digit dialing and matched to cases on sex, age, and geographic region. Data were collected using a standard telephone questionnaire. Occupational factors were based on a detailed history of jobs lasting 6 months or more and job activity, hobby, and specific substance checklists. Several occupational factors, adjusted for age and smoking in conditional multivariate logistic regression analyses, were significantly associated with IPF: farming (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.5); livestock (OR = 2.7, 95% CI: 1.3, 5.5); hairdressing (OR = 4.4, 95% CI: 1.2, 16.3); metal dust (OR = 2.0, 95% CI: 1.0, 4.0); raising birds (OR = 4.7, 95% CI: 1.6, 14.1); stone cutting/polishing (OR = 3.9, 95% CI: 1.2, 12.7); and vegetable dust/animal dust (OR = 4.7, 95% CI: 2.1, 10.4). Interaction was detected between smoking and exposure to livestock (p = 0.06) and farming (p = 0.08). Results confirm previous studies showing increased risk associated with dusty environments.

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Unique Identifier: 20338390 / PubMed Identifier: 10881481

Authors: Ayed AK. Raghunathan R.

Institution: Kuwait University, Faculty of Medicine, Department of Surgery, Kuwait. Adel@hsc.kuniv.edu.kw

Abstract: BACKGROUND: Some patients with diffuse lung disease require a lung biopsy for diagnosis. This study is aimed to compare the clinical results and the efficacy of video-assisted thoracoscopic lung biopsy with the open lung biopsy method for the diagnosis of interstitial lung disease. From January 1996 to December 1998, 61 patients were referred for diagnostic lung biopsy. Thirty two patients were randomly allocated to have a thoracoscopic lung biopsy and twenty nine had an open lung biopsy. Subsequently, various factors were analyzed and compared in both groups. RESULTS: There was no difference between the groups in age and pulmonary function test. Median operative time was 45 minutes for the thoracoscopic biopsies and 60 minutes for the open biopsies (P = 0.009). Median amount of analgesia (Demerol) in the first 24 hours postoperatively was 75 mg. for thoracoscopic biopsies and 150 mg. for open biopsies (P < 0.001). Median duration of insertion of a chest tube in days and 24 hours of pleural drainage was not statistically significant between the two groups. Duration of hospital stay was significantly less for the thoracoscopic biopsy (3 days) compared with an open biopsy (5 days) (P < 0.001). The diagnostic yield of each method was comparable (thoracoscopic biopsy 31/32; open biopsy 27/29) (P = 0.3). Complications occurred in 6/29 of patients undergoing open biopsies and 3/32 patients undergoing thoracoscopic lung biopsies (p = 0.28). There were 2 deaths among patients who had an open lung biopsy. CONCLUSION: Thoracoscopic lung biopsy has some clinical advantages over open biopsy. These findings suggest that thoracoscopic lung biopsy is an acceptable alternative to open lung biopsy for the diagnosis of diffuse interstitial lung diseases.

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Unique Identifier: 20180282 / PubMed Identifier: 10673212

Authors: Anonymous.

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Unique Identifier: 20071288 / PubMed Identifier: 10603633

Authors: Fireman E. Topilsky I. Greif J. Lerman Y. Schwarz Y. Man A. Topilsky M.

Institution: Institute of Pulmonary and Allergic Diseases, Tel-Aviv Sourasky Medical Center, Israel. fireman@fasmc.health.gov.il

Abstract: Bronchoalveolar lavage (BAL), an important tool for evaluating interstitial lung diseases (ILDs), has limited utility due to its invasiveness and the difficulty of performing it in clinically contraindicated patients. We compared BAL with the induced sputum (IS) technique to analyse cells and T lymphocytes in patients with sarcoidosis (SA) and non-granulomatous ILD (NG-ILD). Pulmonary function tests and BAL were performed by conventional methods. IS induction was done 20 sec after inhalation of 3.5% saline with an ultrasonic nebulizer. Giemsa-stained cytopreps were differentially counted. T lymphocyte subsets were analysed by flow activated cell sorter (FACS). Patients with NG-ILD had impaired total lung capacity (TLC). Transbronchial biopsy demonstrated lung fibrosis in NG-ILD and non-caseating granuloma in SA. The differential cell count in both groups demonstrated a significantly lower percentage of neutrophils and a significantly higher percentage of macrophages in BAL than in IS. The IS samples of patients with SA were significantly richer in metachromatic cells and eosinophils, but had a lower percentage of lymphocytes, compared to the BAL samples. The profiles of T cell subsets showed the same pattern, in both samples, in both groups. A CD4/CD8 ratio of 2.5 or greater had a sensitivity of 100% and a specificity of 81.2%, with a positive predictive value of 81.2% to distinguish SA from NG-ILD. IS is an effective non-invasive technique to identify CD4+ inflammation which distinguishes sarcoidosis from other NG-ILDs.

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Unique Identifier: 98019998 / PubMed Identifier: 9357149

Authors: Hira HS. Sharma RK.

Institution: Department of Medicine, Maulana Azad Medical College, New Delhi.

Abstract: Twenty patients of interstitial lung disease (ILD) and same number of healthy adults were selected to monitor arterial hemoglobin oxygen saturation (SaO2) breathing pattern and arrhythmias during sleep. The maximum fall in SaO2 during sleep was 13.1% (10-16%) in ILD patients as compared to 4.8% (3-6%) in controls and the difference was significant (p < 0.005). The ILD patients spent 16.9% of mean total sleep time (TST) below 85% SaO2 and 0.7% of mean TST below 80% SaO2 whereas none of the healthy subjects had SaO2 below 90% during sleep. These patients had more disturbed sleep than controls. Abnormally high breathing frequency demonstrated by ILD patients while awake, was not altered during sleep. Both tidal volume (VT) and minute ventilation (Vmin) decreased by 6.6% and 11.5%, respectively in ILD patients during sleep though it was not significant (p > 0.25) statistically. The respiratory drive was declined during sleep in ILD patients. The percent of tidal volume contributed by rib cage (% RC) lessened during sleep in all the subjects. The ratio of the total excursion of the rib cage and abdomen during inspiration without considering the direction of movement, divided by tidal volume (TCD/VT) revealed asynchronous breathing in ILD patients during sleep. Arrhythmias were found in 6 (30%) of ILD patients and 4 (20%) of control subjects. Observed apnea-hypopnea did not qualify for sleep apnea syndrome in any case.

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Unique Identifier: 97154601 / PubMed Identifier: 9001319

Authors: Baumgartner KB. Samet JM. Stidley CA. Colby TV. Waldron JA.

Institution: Division of Epidemiology and Cancer Control, University of New Mexico Health Sciences Center, Albuquerque 87131-5306, USA.

Abstract: We conducted a multicenter case-control study of clinically and histologically diagnosed idiopathic pulmonary fibrosis (IPF), a chronic diffuse interstitial lung disease of unknown cause. The study included 248 cases, and 491 control subjects identified through random-digit dialing, matched to cases in sex, age, and geographic region. Telephone interviews were conducted with both cases and controls to collect information on potential risk factors for IPF, including smoking and household, occupational, and environmental exposures. Pulmonary function tests, X-rays, computed tomographic (CT) scans of the chest, and lung biopsy reports were submitted by referring centers to support the diagnoses. An a priori hypothesis that smoking is associated with IPF was examined with conditional logistic regression analyses. More cases (72%) than control subjects (63%) had a history of ever smoking. The odds ratio (OR) for ever smoking was 1.6 (95% CI: 1.1 to 2.4). Risk was significantly elevated for former smokers (OR = 1.9; 95% CI: 1.3 to 2.9) and for smokers with 21 to 40 pack-yr (OR = 2.3; 95% CI: 1.3 to 3.8). A history of smoking is associated with an increased risk for the development of IPF. Although there was no clear exposure-response pattern with cumulative consumption of cigarettes, there was a trend for time since cessation of smoking, with the highest risk for those who had most recently quit.

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Unique Identifier: 94008115 / PubMed Identifier: 8404183

Authors: Nishimura K. Izumi T. Kitaichi M. Nagai S. Itoh H.

Institution: Chest Disease Research Institute, Kyoto University, Japan.

Abstract: The purpose of this study was to evaluate the role of high-resolution computed tomography (HRCT) in the clinical diagnosis of diffuse infiltrative lung disease (DILD). Diagnostic accuracy was compared using both chest radiography and HRCT. One hundred thirty-four cases of DILD, representing 21 different diseases, were selected for study, and the disease state was confirmed either histologically or microbiologically. The HRCT images and chest radiographs, available in all cases, were reviewed separately and in random order by 20 physicians who were provided only with information on each patient's age and sex. Overall, a correct first-choice diagnosis was made in 38 percent using radiographs and in 46 percent using HRCT images (p < 0.01). The correct diagnosis was among the top three choices in 49 percent when chest radiographs were used, and in 59 percent when HRCT images were viewed (p < 0.01). The correct first-choice diagnosis increased remarkably when the HRCT was used in usual interstitial pneumonia, sarcoidosis, alveolar proteinosis, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis, and pulmonary lymphangiomyomatosis. High-resolution computed tomography was confirmed to be superior to conventional radiography in the accurate diagnosis of DILD in clinical practice.

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Unique Identifier: 92027163 / PubMed Identifier: 1718192

Authors: Cherniack RM. Colby TV. Flint A. Thurlbeck WM. Waldron J. Ackerson L. King TE Jr.

Institution: Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.

Abstract: The diagnosis and classification of most interstitial lung diseases requires histologic evaluation of lung tissue, obtained by an open lung biopsy to confirm the diagnosis. In addition, it is generally accepted that response to therapy in idiopathic pulmonary fibrosis (IPF) is related to the relative degree of cellularity and fibrosis present. Because only a qualitative assessment of the relative extent and severity of these changes is generally provided, correlation with clinical and physiologic alterations is difficult. This report describes results of a semiquantitative assessment by four pathologists of inflammatory/exudative changes, fibrotic/reparative changes, and airway alterations, in addition to an overall assessment of cellularity and fibrosis in 50 patients with IPF. In 10 randomly selected biopsies examined twice in a blinded fashion, absolute agreement between assessments for a given pathologist varied between 54 and 64% (mean = 57.5%) and in the majority of instances the agreement was greater than would have occurred by chance. There was good agreement for most variables across the four raters on the 101 samples. The mean score for some of the parameters reported by a given rater deviated occasionally from those of the other raters, but no single rater was consistently different from the other raters. A principal component factor analysis revealed that the pathologic features fell into four general groupings: alveolar wall metaplasia, fibrosis, honeycombing, smooth muscle, and vascular changes fell into one group; severity and extent of cellularity in the alveolar wall into a second group; severity and extent of cellularity in the alveolar space into a third group; and interstitial young connective tissue along with granulation tissue in the airways formed the fourth group.(ABSTRACT TRUNCATED AT 250 WORDS)