Tunnel excavation triggering pulmonary sarcoidosis.

CONTEXT: A definite cause of sarcoidosis has not been identified, however past research suggests that environmental factors may be triggers of the granulomatous response in genetically susceptible individuals. CASE PRESENTATION: A 22-year-old male non-smoker, presented with progressive exertional dyspnea and cough of 3 months duration. One year before, when he started working in tunnel excavation, he had a normal chest radiograph. Chest imaging revealed bilateral nodules and masses of peribronchovascular distribution plus mediastinal lymphadenomegaly. Histologic lymph node analysis revealed non-caseating confluent granulomas. Sarcoidosis was diagnosed. The patient was treated with corticosteroids and advised to change jobs. Complete remission of the disease was achieved and persisted for at least one year without steroid treatment. DISCUSSION: Sarcoidosis is believed to have environmental triggers. The timing of the onset of sarcoidosis in this patient following intensive exposure to tunnel dust suggests an environmental contribution. The recognition that sarcoidosis may have occupational triggers have medical, employment, and legal implications.

Comparison of two questionnaires which measure the health-related quality of life of idiopathic pulmonary fibrosis patients.

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.

Histochemical evaluation of lung collagen content in acute and chronic interstitial diseases.

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.

Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP).

BACKGROUND/AIMS: The pathogenesis of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), a chronic and incurable human respiratory disease, is not well established. This study was designed to investigate whether the apoptosis of type II pneumocytes could be the precipitating factor in the pathogenesis of IPF. METHODS: Nineteen specimens obtained by retrospective review of the medical and pathological records of 55 patients with IPF, four normal subjects, and 10 disease control lungs were analysed. The selected specimens had normal alveoli with intervening patchy scarring of the lung parenchyma, fulfilling the pathological criteria for UIP. To identify individual cells undergoing apoptosis in the normal alveoli, electron microscopy and in situ end labelling of fragmented DNA were performed on paraffin was embedded sections using digoxigenin-11-dUTP and the enzyme terminal deoxynucleotidyl transferase. RESULTS: Apoptosis was detected in the normal alveoli of 17 of the 19 patients with IPF/UIP and was absent in the controls. Electron microscopy demonstrated apoptotic changes in type II pneumocytes. These results indicate that apoptotic type II pneumocyte death occurs in normal alveoli of IPF/UIP and could be the principal cause of several events that account for the histological, clinical, and functional alterations seen in IPF/UIP. CONCLUSIONS: In conclusion, numerous type II pneumocytes from the normal alveoli of most patients with IPF/UIP actively undergo programmed cell death. This finding may shed new light on the pathogenesis of this disease, with implications mainly for the treatment of affected patients.

Chronic amiodarone ingestion induces pulmonary toxicity in rats.

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.

Epipericardial fat necrosis: an underdiagnosed condition.

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.

Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis.

Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 ± 1.11) to UIP (23.45 ± 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.

Effects of proportional assisted ventilation on exercise performance in idiopathic pulmonary fibrosis patients.

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.

Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis

Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 ± 1.11) to UIP (23.45 ± 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.

Collagen and elastic system in the remodelling process of major types of idiopathic interstitial pneumonias (IIP).

AIMS: Structural remodelling in acute and chronic idiopathic interstitial pneumonia (IIP) has been extensively investigated, but little attention has been directed to the elastic tissue in these situations. The aim of this study was to determine whether elastic deposition accompanies collagen deposition in the four major histological patterns of IIP: diffuse alveolar damage (DAD), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). METHODS AND RESULTS: We measured, by image analysis, the content of fibres of the collagenous and elastic systems of the alveolar septum in histological slides of open lung biopsies, using the picrosirius-polarization method and Weigert's resorcin-fuchsin stain, respectively. Five groups were studied: 10 cases of DAD; nine cases of OP; nine cases of NSIP; and 10 cases of UIP. Four normal lungs were used for comparison. The content of collagen fibres was significantly higher in UIP when compared to DAD, NSIP, OP and normal lung. The content of elastic fibres was increased in comparison with normal lungs but this was not significantly different among the histological patterns. CONCLUSION: Acute and chronic IIP cause a similar increase in the collagen and elastic contents of the lungs, representing a process of 'fibroelastosis' rather than an exclusive process of fibrosis. A profibrogenic mechanism is responsible for the unparallelled collagen augmentation observed in UIP subjects, the nature of which is yet to be determined.

Solitary plasmacytoma of the trachea treated by loop resection and laser therapy.

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.

[Tuberculous pleural effusion: clinical and laboratory evaluation]. / Derrame pleural, tuberculoso: avaliação clínca e laboratorial.

Clinical data concerning 44 patients with pleural tuberculosis are presented. The average age was 35 years. The main symptoms were fever (41/44), chest pain (41/44) and weight loss (34/44). In all but one case the pleural effusion was unilateral without preference for one or other hemithorax. In ten patients (23%) parenchymal lesions could be recognized on chest roentgenograms. Three patients had coexisting active pulmonary disease with positive sputum culture. Forty-nine pleural biopsies were performed in 44 patients. The culture of pleural tissue was positive in 75%, and culture of pleural fluid in 22.5%. The pleural fluid was exudative with fluid-to-serum ratios of protein and LDH exceeding 0.5 and 0.6 respectively. The cellular characterization of pleural fluid has demonstrated predominance of lymphocytes and scarcity of mesothelial cells. The patients received adequate treatment with excellent results, exhibiting an increased weight, increased hemoglobin and decreased ESR. The development of residual pleural thickening occurred in 23 out of 44 cases.

[Kidney failure as a complication of the treatment of pulmonary paracoccidioidomycosis]. / Insuficiência renal como complicação do tratamento da paracoccidioidomicose pulmonar.

Sulfadiazine is one of the drugs of choice in the treatment of paracoccidioidomycosis. Side effects are uncommon. Cutaneous and gastrointestinal reactions and rarely leucopenia and jaundice may occur. A patient on sulfadiazine 6 g daily exhibiting a good response is reported. On the 12th day, he presented an intense abdominal pain and reduced urinary output. An ultrasonography revealed diffuse calculosis in urinary tract. Peritoneal dialysis, urinary alkalinization and rehydration were instituted with complete restoration of renal function. This case illustrates the importance of an adequate hydratation of patients receiving sulfadiazine, a simple measure in the prevention of this uncommon complication which carries a high morbidity.

Obstructive respiratory failure in cicatricial pemphigoid.

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.

Interstitial lung disease in primary Sjögren's syndrome. Clinical-pathological evaluation and response to treatment.

Interstitial disease is a recognized form of lung involvement in primary Sjögren's syndrome in which frequency and severity have not yet been established. We studied 20 patients 61.2 +/- 36.4 mo after the first symptoms of the syndrome that fulfilled criteria for both xerostomia and xerophtalmia. Eighteen patients exhibited pulmonary symptoms; nine presented a restrictive functional pattern. The chest roentgenogram disclosed interstitial involvement in nine patients. Gallium-67 lung scan presented hypercaptation in 15 of 19 patients studied. Thirteen patients who submitted to bronchoalveolar lavage presented higher cell counts with increases of lymphocytes and/or polymorphonuclear cells. All patients had abnormal results in at least one of the above. Lung biopsy, undertaken in 12 patients, showed a whole spectrum of interstitial disease, from a follicular bronchiolitis to a lymphoid interstitial pneumonia and finally fibrosis with honeycombing. One patient presented with associated sarcoid granulomas. We treated 11 patients with an azathioprine-based regimen and found a significant improvement in the forced vital capacity (p < 0.05) after at least 6 mo when compared with nontreated patients. We conclude that the frequency of interstitial lung disease is high in Sjögren's syndrome and that an azathioprine-based treatment can favorably change the outcome in this population.

Beneficial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation.

Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals submitted to artificial ventilation. To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome (ARDS) submitted to conventional mechanical ventilation (MV), we evaluated the impact of a new ventilatory strategy directed at minimizing "cyclic parenchymal stretch." After receiving pre-established levels of hemodynamic, infectious, and general care, 28 patients with early ARDS were randomly assigned to receive either MV based on a new approach (NA, consisting of maintenance of end-expiratory pressures above the lower inflection point of the P x V curve, VT < 6 ml/kg, peak pressures < 40 cm H2O, permissive hypercapnia, and stepwise utilization of pressure-limited modes) or a conventional approach (C = conventional volume-cycled ventilation, VT = 12 ml/kg, minimum PEEP guided by FIO2 and hemodynamics and normal PaCO2 levels). Fifteen patients were selected to receive NA, exhibiting a better evolution of the PaO2/FIO2 ratio (p < 0.0001) and of compliance (p = 0.0018), requiring shorter periods under FIO2 > 50% (p = 0.001) and a lower FIO2 at the day of death (p = 0.0002). After correcting for baseline imbalances in APACHE II, we observed a higher weaning rate in NA (p = 0.014) but not a significantly improved survival (overall mortality: 5/15 in NA versus 7/13 in C, p = 0.45). We concluded that the NA ventilatory strategy can markedly improve the lung function in patients with ARDS, increasing the chances of early weaning and lung recovery during mechanical ventilation.