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Objective: Epipericardial fat necrosis (EFN) is an uncommon benign and self-limited condition that leads patients to the emergency department (ED) owing to the onset of acute pleuritic chest pain. The aim of this study was to describe the cases of this disease in our institution and to illustrate the associated clinical and radiological findings. Methods: We reviewed 3604 chest scans referred by the ED from November 2011 to July 2013. Patients diagnosed with epipericardial necrosis had their medical records and original tomography reports analysed. Results: Chest pain was the primary complaint in 426 patients; 11 of them had definitive EFN findings characterized by a round soft-tissue attenuation lesion with a varying degree of strands. Ail patients presented with pleuritic chest pain on the same side as the lesion. Pericardial thickening, pleural effusion and mild atelectasis were the associated tomography findings. Cardiac enzyme and D-dimer tests performed during the episode were normal in all cases. 27% of the cases only were correctly diagnosed with EFN at the time of presentation. Conclusion: EFN is a benign inflammatory condition frequentiy overlooked in the ED by physicians and radiologists but is an important factor in the differential diagnosis of patients with acute chest pain. Advances in knowledge: The article adds clinically and radiologically useful information about the condition and displays the importance of making the correct diagnosis to avoid unnecessary examinations. [ABSTRACT FROM AUTHOR]

Summary: Rationale: Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. Objectives: We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. Methods: We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Measurements and main results: Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa''s classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; p <0.01) and among patients with severe motor dysfunction (90% vs. 35%; p <0.001). Conclusions: Although we were not able to prove a causal relationship between esophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease. [Copyright &y& Elsevier]

A 20 year old woman died of respiratory failure due to cicatricial pemphigoid of the trachea and bronchi. This is the first case with the lower airways affected to be reported. [ABSTRACT FROM PUBLISHER]

A 53 year old woman with respiratory failure and stridor caused by a tracheal plasmacytoma was treated by endoscopic loop polypectomy and neodymium YAG laser therapy, followed by local irradiation. Two years later there was no evidence of recurrence of disease. [ABSTRACT FROM PUBLISHER]

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and frequently fatal disease. Currently there are national and multinational registries in Europe, United States, Australia and China to better understand the magnitude of the problem and the characteristics of the IPF patients. However, there are no national or regional registries in Latin America, so the objective of this study was to carry out a Latin American registry that would allow the identification of IPF patients in our region., Methodology: A system consisting of 3 levels of control was designed, ensuring that patients met the diagnostic criteria for IPF according to international guidelines ATS/ERS/ALAT/JRS 2011. Demographic, clinical, serological, functional, tomographic, histological and treatment variables were recorded through a digital platform., Results: 761 IPF patients from 14 Latin American countries were included for analysis, 74.7% were male, with a mean age of 71.9+8.3 years. In general there was a long period of symptoms before definitive diagnosis (median 1 year). In functional tests, an average reduction of FVC (70.9%) and DLCO (53.7%) was detected. 72% received at least one antifibrotic drug (pirfenidone or nintedanib) and 11.2% of the patients had an acute exacerbation, of which 38 (45.2%) died from this cause., Conclusions: Like other registries, we found that there is difficulty in the recognition and excessive delay in the diagnosis of IPF in Latin America. Most of the patients in REFIPI received antifibrotics; these were well tolerated and associated with fewer adverse events than those reported in clinical trials., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Question Addressed by the Study: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD., Methods: Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques., Results: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001)., Answer to the Question: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients., Competing Interests: Conflict of interest: P-A. Juge has nothing to disclose. Conflict of interest: J.S. Lee reports grants from NIH, personal fees for advisory board work from Genentech and Celgene, outside the submitted work. Conflict of interest: J. Lau has nothing to disclose. Conflict of interest: L. Kawano-Dourado has nothing to disclose. Conflict of interest: J. Rojas-Serrano has nothing to disclose. Conflict of interest: M. Sebastiani has nothing to disclose. Conflict of interest: G. Koduri has nothing to disclose. Conflict of interest: E. Matteson has nothing to disclose. Conflict of interest: K. Bonfiglioli has nothing to disclose. Conflict of interest: M. Sawamura has nothing to disclose. Conflict of interest: R. Kairalla has nothing to disclose. Conflict of interest: L. Cavagna has nothing to disclose. Conflict of interest: E. Bozzalla Cassione has nothing to disclose. Conflict of interest: A. Manfredi has nothing to disclose. Conflict of interest: M. Mejia has nothing to disclose. Conflict of interest: P. Rodríguez-Henriquez has nothing to disclose. Conflict of interest: M.I. González Pérez has nothing to disclose. Conflict of interest: R. Falfán-Valencia has nothing to disclose. Conflict of interest: I. Buendia-Roldán has nothing to disclose. Conflict of interest: G. Pérez-Rubio has nothing to disclose. Conflict of interest: E. Ebstein reports personal fees from Sanofi, outside the submitted work. Conflict of interest: S. Gazal has nothing to disclose. Conflict of interest: R. Borie reports grants and personal fees for lectures from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: S. Ottaviani has nothing to disclose. Conflict of interest: C. Kannengiesser has nothing to disclose. Conflict of interest: B. Wallaert reports grants and personal fees for advisory board work and meeting attendance from Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: Y. Uzunhan reports personal fees from Roche and Boehringer Ingelheim, non-financial support from Oxyvie, outside the submitted work. Conflict of interest: H. Nunes has nothing to disclose. Conflict of interest: D. Valeyre reports personal fees for advisory board work from Roche and Boehringer Ingelheim, personal fees for lectures from AstraZeneca, outside the submitted work. Conflict of interest: N. Saidenberg-Kermanac'h has nothing to disclose. Conflict of interest: M-C. Boissier has nothing to disclose. Conflict of interest: L. Wemeau-Stervinou reports personal fees for lectures and travel support from Roche, personal fees for lectures and advisory board work, and travel support from Boehringer-Ingelheim, personal fees for lectures from Janssen-Cilag and Bristol-Myers-Squibb, outside the submitted work. Conflict of interest: R.M. Flipo reports grants and personal fees from Roche Chugai, Abbvie and Pfizer, personal fees from Bristol-Meyers Squibb, outside the submitted work. Conflict of interest: S. Marchand-Adam reports fees for research, lectures, meeting attendance, consultancy and advisory board work from Roche, Boehringer Ingelheim and Novartis, outside the submitted work. Conflict of interest: P. Richette reports personal fees from Ipsen/Menarini, AstraZeneca, Savient and Grünenthal, outside the submitted work. Conflict of interest: Y. Allanore reports personal fees from Actelion, Bayer, Bristol-Myers Squibb, Boehringer and Inventiva, grants from Sanofi and Roche, outside the submitted work. Conflict of interest: C. Dromer has nothing to disclose. Conflict of interest: M-E. Truchetet has nothing to disclose. Conflict of interest: C. Richez has nothing to disclose. Conflict of interest: T. Schaeverbeke has nothing to disclose. Conflict of interest: H. Lioté has nothing to disclose. Conflict of interest: G. Thabut reports personal fees from AstraZeneca, outside the submitted work. Conflict of interest: K.D. Deane has nothing to disclose. Conflict of interest: J. Solomon has nothing to disclose. Conflict of interest: T. Doyle has nothing to disclose. Conflict of interest: J.H. Ryu has nothing to disclose. Conflict of interest: I. Rosas reports personal fees for advisory board work from Genentech, Boehringer and Three Lakes Partners, outside the submitted work. Conflict of interest: V.M. Holers reports grants from NIH/NIAID (U01 Grant), during the conduct of the study. Conflict of interest: C. Boileau has nothing to disclose. Conflict of interest: M-P. Debray reports personal fees and non-financial support for travel to meetings from Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: R. Porcher has nothing to disclose. Conflict of interest: D.A. Schwartz reports grants from NIH-NHLBI (P01 HL092870, R01 HL097163, R33 HL120770 and UH2 HL123442) and DOD Focused Program (W81XWH-17-1-0597), during the conduct of the study; personal fees for consultancy and advisory board work from NuMedii, Inc., and is an employee of Eleven P15, Inc., outside the submitted work; and has a patent Compositions and Methods of Treating or Preventing Fibrotic Diseases pending, a patent Biomarkers for the Diagnosis and Treatment of Fibrotic Lung Disease pending, and a patent Methods and Compositions for Risk Prediction, Diagnosis, Prognosis, and Treatment of Pulmonary Disorders issued. Conflict of interest: R. Vassallo reports grants from Pfizer, Bristol-Myers-Squibb and SunPharma, outside the submitted work. Conflict of interest: B. Crestani reports grants from Apellis and MedImmune, grants and personal fees for lectures from Boehringer Ingelheim and Roche, personal fees for lectures from AstraZeneca and Sanofi, outside the submitted work. Conflict of interest: P. Dieudé reports fees for consultancy from Pfizer, Abbvie and MSD, grants and personal fees for consultancy and lectures from Roche, Chugai and BMS, outside the submitted work., (Copyright ©ERS 2021.)

Progressive fibrotic interstitial lung diseases (ILDs) are characterised by major reductions in quality of life and survival and have similarities to certain malignancies. However, palliative care expertise is conspicuously inaccessible to many patients with ILD. Unmet patient and caregiver needs include effective pharmacological and psychosocial interventions to improve quality of life throughout the disease course, sensitive advanced care planning, and timely patient-centred end-of-life care. The incorrect perception that palliative care is synonymous with end-of-life care, with no role earlier in the course of ILD, has created a culture of neglect. Interventions that aim to improve life expectancy are often prioritised without rigorous assessment of the individual's health and psychosocial needs, thereby inadvertently reducing quality of life. As in malignant disorders, radical interventions to slow disease progression and palliative measures to improve quality of life should both be prioritised. Efficient patient-centred models of palliative care must be validated, taking into account religious and cultural differences, as well as variability of resources. Effective implementation of palliative care for ILD will require multidisciplinary participation from clinicians, specialist nurses, psychologists, social workers, and, in some countries, non-governmental faith and community-based organisations with access to palliative care expertise., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Epipericardial fat necrosis (EFN) is an uncommon benign and self-limited condition that leads patients to the emergency department (ED) owing to the onset of acute pleuritic chest pain. The aim of this study was to describe the cases of this disease in our institution and to illustrate the associated clinical and radiological findings., Methods: We reviewed 3604 chest scans referred by the ED from November 2011 to July 2013. Patients diagnosed with epipericardial necrosis had their medical records and original tomography reports analysed., Results: Chest pain was the primary complaint in 426 patients; 11 of them had definitive EFN findings characterized by a round soft-tissue attenuation lesion with a varying degree of strands. All patients presented with pleuritic chest pain on the same side as the lesion. Pericardial thickening, pleural effusion and mild atelectasis were the associated tomography findings. Cardiac enzyme and D-dimer tests performed during the episode were normal in all cases. 27% of the cases only were correctly diagnosed with EFN at the time of presentation., Conclusion: EFN is a benign inflammatory condition frequently overlooked in the ED by physicians and radiologists but is an important factor in the differential diagnosis of patients with acute chest pain., Advances in Knowledge: The article adds clinically and radiologically useful information about the condition and displays the importance of making the correct diagnosis to avoid unnecessary examinations.

Objective: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) is one of the leading causes of mortality. We undertook this study to analyze the gene expression of lung tissue in a prospective cohort of patients with SSc-related ILD and to compare it with that in control lungs and with 2 prospective clinical parameters in order to understand the molecular pathways implicated in progressive lung disease., Methods: Lung tissue was obtained by open lung biopsy in 28 consecutive patients with SSc-related ILD and in 4 controls. High-resolution computed tomography (HRCT) and pulmonary function testing (PFT) were performed at baseline and 2-3 years after treatment based on lung histologic classification. Microarray analysis was performed, and the results were correlated with changes in the HRCT score (FibMax) and PFT values. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to confirm differential levels of messenger RNA and protein., Results: Lung microarray data distinguished patients with SSc-related ILD from healthy controls. In the lungs of patients with SSc-related ILD who had nonspecific interstitial pneumonia (NSIP), expressed genes included macrophage markers, chemokines, collagen, and transforming growth factor β (TGFβ)- and interferon (IFN)-regulated genes. Expression of these genes correlated with progressive lung fibrosis defined by the change in FibMax. Immunohistochemistry confirmed increased markers of collagen (COL1A1), IFN (OAS1 and IFI44), and macrophages (CCL18 and CD163), and the positive correlation with the change in FibMax was confirmed by qPCR in a larger group of SSc patients with NSIP. Several genes correlated with both the change in FibMax (r > 0.4) and the change in % predicted forced vital capacity (r < -0.1), including IFN and macrophage markers, chemokines, and heat-shock proteins., Conclusion: These results highlight major pathogenic pathways relevant to progressive pulmonary fibrosis in SSc-related ILD: macrophage emigration and activation, and up-regulated expression of TGFβ- and IFN-regulated genes., (Copyright © 2014 by the American College of Rheumatology.)

Background: Few studies have addressed small airway (SA) histopathological changes and their possible role in the remodeling process in idiopathic interstitial pneumonias., Objectives: To study morphological, morphometrical and immunohistochemical features of SA in idiopathic pulmonary fibrosis (usual interstitial pneumonia, UIP) and nonspecific interstitial pneumonia (NSIP)., Methods: We analyzed SA pathology in lung biopsies from 29 patients with UIP and 8 with NSIP. Biopsies were compared with lung tissue from 13 patients with constrictive bronchiolitis (CB) as positive controls and 10 normal autopsied control lungs. We semi-quantitatively analyzed SA structure, inflammation, architectural features and the bronchiolar epithelial immunohistochemical expression of TGF-beta, MMP-2, 7, 9, and their tissue inhibitors (TIMP-1, 2)., Results: Compared to controls, patients with UIP, NSIP and CB presented increased bronchiolar inflammation, peribronchiolar inflammation and fibrosis and decreased luminal areas. UIP patients had thicker walls due to an increase in most airway compartments. NSIP patients presented increased epithelial areas, whereas patients with CB had larger inner wall areas. All of the groups studied presented increased bronchiolar expression of MMP-7 and MMP-9, compared to the controls., Conclusion: We conclude that SAs are pathologically altered and may take part in the lung-remodeling process in idiopathic interstitial pneumonias., (Copyright 2009 S. Karger AG, Basel.)

Background: Patients with idiopathic pulmonary fibrosis (IPF) present an important ventilatory limitation reducing their exercise capacity. Non-invasive ventilatory support has been shown to improve exercise capacity in patients with obstructive diseases; however, its effect on IPF patients remains unknown., Objective: The present study assessed the effect of ventilatory support using proportional assist ventilation (PAV) on exercise capacity in patients with IPF., Methods: Ten patients (61.2+/-9.2 year-old) were submitted to a cardiopulmonary exercise testing, plethysmography and three submaximal exercise tests (60% of maximum load): without ventilatory support, with continuous positive airway pressure (CPAP) and PAV. Submaximal tests were performed randomly and exercise capacity, cardiovascular and ventilatory response as well as breathlessness subjective perception were evaluated. Lactate plasmatic levels were obtained before and after submaximal exercise., Results: Our data show that patients presented a limited exercise capacity (9.7+/-3.8 mL O(2)/kg/min). Submaximal test was increased in patients with PAV compared with CPAP and without ventilatory support (respectively, 11.1+/-8.8 min, 5.6+/-4.7 and 4.5+/-3.8 min; p<0.05). An improved arterial oxygenation and lower subjective perception to effort was also observed in patients with IPF when exercise was performed with PAV (p<0.05). IPF patients performing submaximal exercise with PAV also presented a lower heart rate during exercise, although systolic and diastolic pressures were not different among submaximal tests. Our results suggest that PAV can increase exercise tolerance and decrease dyspnoea and cardiac effort in patients with idiopathic pulmonary fibrosis., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The objective of the present study was to determine if there is a health-related quality of life (HRQL) instrument, generic or specific, that better represents functional capacity dysfunction in idiopathic pulmonary fibrosis (IPF) patients. HRQL was evaluated in 20 IPF patients using generic and specific questionnaires (Medical Outcomes Short Form 36 (SF-36) and Saint George's Respiratory Questionnaire (SGRQ), respectively). Functional status was evaluated by pulmonary function tests, 6-min walking distance test (6MWDT) and dyspnea indexes (baseline dyspnea index) at rest and after exercise (modified Borg scale). There was a restrictive pattern with impairment of diffusion capacity (total lung capacity, TLC = 71.5 +/- 15.6%, forced vital capacity = 70.4 +/- 19.4%, and carbon monoxide diffusing capacity = 41.5 +/- 16.2% of predicted value), a reduction in exercise capacity (6MWDT = 435.6 +/- 95.5 m) and an increase of perceived dyspnea score at rest and during exercise (6 +/- 2.5 and 7.1 +/- 1.3, respectively). Both questionnaires presented correlation with some functional parameters (TLC, forced expiratory volume in 1 s and carbon monoxide diffusing capacity) and the best correlation was with TLC. Almost all of the SGRQ domains presented a strong correlation with functional status, while in SF-36 only physical function and vitality presented a good correlation with functional status. Dyspnea index at rest and 6MWDT also presented a good correlation with HRQL. Our results suggest that a specific instead of a generic questionnaire is a more appropriate instrument for HRQL evaluation in IPF patients and that TLC is the functional parameter showing best correlation with HRQL.

Background: In patients with the acute respiratory distress syndrome, massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury. We determined whether a ventilatory strategy designed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome., Methods: We randomly assigned 53 patients with early acute respiratory distress syndrome (including 28 described previously), all of whom were receiving identical hemodynamic and general support, to conventional or protective mechanical ventilation. Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure (PEEP) for acceptable oxygenation, with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels (35 to 38 mm Hg). Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve, a tidal volume of less than 6 ml per kilogram, driving pressures of less than 20 cm of water above the PEEP value, permissive hypercapnia, and preferential use of pressure-limited ventilatory modes., Results: After 28 days, 11 of 29 patients (38 percent) in the protective-ventilation group had died, as compared with 17 of 24 (71 percent) in the conventional-ventilation group (P<0.001). The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group (P=0.005): the rates of clinical barotrauma were 7 percent and 42 percent, respectively (P=0.02), despite the use of higher PEEP and mean airway pressures in the protective-ventilation group. The difference in survival to hospital discharge was not significant; 13 of 29 patients (45 percent) in the protective-ventilation group died in the hospital, as compared with 17 of 24 in the conventional-ventilation group (71 percent, P=0.37)., Conclusions: As compared with conventional ventilation, the protective strategy was associated with improved survival at 28 days, a higher rate of weaning from mechanical ventilation, and a lower rate of barotrauma in patients with the acute respiratory distress syndrome. Protective ventilation was not associated with a higher rate of survival to hospital discharge.

The associated use of permissive hypercapnia (PHY) and high PEEP levels (PEEP(IDEAL)) has been recently indicated as part of a lung-protective-approach (LPA) in acute respiratory distress syndrome (ARDS). However, the net hemodynamic effect produced by this association is not known. We analyzed the temporal hemodynamic effects of this combined strategy in 48 patients (mean age 34 +/- 13 yr) with ARDS, focusing on its immediate (after 1 h), early (first 36 h), and late (2nd-7th d) consequences. Twenty-five patients were submitted to LPA--with the combined use of permissive hypercapnia (PHY), VT < 6 ml/kg, distending pressures above PEEP < 20 cm H2O, and PEEP 2 cm H2O above the lower inflection point on the static inspiratory P-V curve (P(FLEX))- and 23 control patients were submitted to conventional mechanical ventilation. LPA was initiated at once, resulting in an immediate increase in heart rate (p = 0.0002), cardiac output (p = 0.0002), oxygen delivery (DO2l, p = 0.0003), and mixed venous Po2 (p = 0.0006), with a maintained systemic oxygen consumption (p = 0.52). The mean pulmonary arterial pressure markedly increased (mean increment 8.8 mm Hg; p < 0.0001), but the pulmonary vascular resistance did not change (p = 0.32). Cardiac filling pressures increased (p < 0.001) and the systemic vascular resistance fell (p = 0.003). All these alterations were progressively attenuated in the course of the first 36 h, despite persisting hypercapnia. Plasma lactate suffered a progressive decrement along the early period in LPA but not in control patients (p < 0.0001). No hemodynamic consequences of LPA were noticed in the late period and renal function was preserved. A multivariate analysis suggested that these acute hyperdynamic effects were related to respiratory acidosis, with no depressant effects ascribed to high PEEP levels. In contrast, high plateau pressures were associated with cardiovascular depression. Thus, as long as sufficiently low distending pressures are concomitantly applied, the sudden installation of PHY plus PEEP(IDEAL) induces a transitory hyperdynamic state and pulmonary hypertension without harmful consequences to this young ARDS population.

Patients who receive amiodarone may develop interstitial pulmonary disease. The objective of the present study was to develop an experimental model of interstitial pulmonary disease in rats based on the chronic oral administration of amiodarone diluted in water ad libitum. A total of 97 three-month old male Wistar rats weighing 133-167 g (control and intoxicated) were studied after daily administration of amiodarone (about 50 mg/kg) for 3 weeks and 3, 6, and 13 months. We carried out conventional histopathologic evaluation, morphometric studies of the alveolar wall, transmission electron microscopy, measurement of pulmonary volumes and forced expiratory flows, and computed respiratory system resistance and elastance during spontaneous breath cycles. Chronic ingestion of amiodarone by rats produced pulmonary disease that started as a phospholipidosis, as early as 3 weeks after the use of the drug. After 6, and mainly after 13 months, a focal inflammatory reaction with reactive alveolar epithelium was observed. Signals of a concomitant repair process were also present, but fibrosis was visible only by electron microscopy. The physiologic dysfunction could be identified after 13 months; expiratory flow (ml/sec) limitation and an increased respiratory system elastance (cmH2O/ml) were the main functional changes, respectively 10.8 (forced expiratory mean flow between 0-25% of forced vital capacity) and 5.36 in treated animals vs 13.3 and 3.65 in controls, reported as mean +/- SD for 6 animals in each group. A body of evidence suggests that amiodarone may cause changes in lung phospholipid metabolism that may be responsible for a part of the functional derangement observed in this study.

The collagen content and its aggregational state was histochemically measured in interstitial lung diseases. Open chest biopsies of ten patients with adult respiratory distress syndrome, seven patients with sarcoidosis, and nine patients with fibrosis associated with connective tissue diseases and with idiopathic pulmonary fibrosis (IPF/CTD) were compared with eight samples of normal lungs. The collagen content of diseased lungs was significantly increased when compared to control lungs, but no difference was observed among the pathologic groups. The analysis of collagen aggregational state showed maximal aggregation in IPF/CTD, followed by sarcoidosis, ARDS, and control lungs, in decreasing order. The results suggest that measurement of collagen aggregation coupled with collagen content could be used in the evaluation of interstitial lung disease and encourage the use of new techniques in order to better explain the dramatic histologic and functional alterations observed in many disease-associated lung processes.