You are describing sarcoidosis.

A 30-year-old donkey man undergoes a chest X-ray to formalize an employment contract in a company. The X-ray shows a bilateral interstitial pattern of reticular type, bilateral hilar and mediastinal adenopathies. Bronchofibroscopy with bronchoalveolar lavage is indicated and the cell count shows the following results: lymphocytes 50%, histiocytes 40%, eosinophils 2%, polymorphonuclear 8% and CD4/Cd8 ratio 5 What is the most likely diagnosis?

Bronchoalveolar lavage in sarcoidosis.

There is no single cell type present in bronchoalveolar lavage (BAL) fluid that appears to be predictive for sarcoidosis. However, BAL fluid analysis can be very helpful in the differential diagnosis. A grouping of features, an elevated total cell count, predominantly lymphocytes, together with a nearly normal percentage of eosinophils and polymorphonuclear neutrophils and the absence of plasma cells, distinguish the most likely diagnosis of sarcoidosis from the most common interstitial lung diseases, extrinsic allergic alveolitis (EAA), nonspecific interstitial pneumonia (NSIP), and idiopathic pulmonary fibrosis (IPF). In sarcoidosis the majority of cases have an increased number of lymphocytes and a normal amount of eosinophils and neutrophils. Disease presentation or activity at the time the BAL is performed as well as the smoking status is crucial for interpretation of individual BAL fluid analysis results. In severe cases the number of neutrophils can be increased as well. For an individual case the CD4:CD8 ratio is of less importance because it can be increased, normal, and even decreased. In the follow-up depicting prognosis and response to treatment, BAL fluid analysis has less clinical relevance.

[A case of pleural sarcoidosis in which vats lung biopsy, obtained pleural and pulmonary lesions].

Here we report a case that was diagnosed as sarcoidosis but required differential diagnosis from pneumoconiosis. A 51-year-old asymptomatic man, who showed signs of bilateral hilar lymphadenopathy (BHL) on a chest X-ray taken during a medical check, was given a diagnosis of sarcoidosis, based on the results of mediastinoscopic mediastinal lymph node biopsy. Because of the presence of large and small nodular lesions adjacent to the pleura extending from the bilateral upper lobes into the lung field, and continuous bead-like, small nodular lesions in the right interlobar pleura, pleural sarcoidosis was suspected and thoracoscopy was performed. Macroscopically, multiple grayish-white nodules with distinct margins, up to 1cm in diameter surrounded by a proliferation of capillaries were found in the pleura, particularly in the upper lobes. Lesions were also scattered over the interlobar pleura and diaphragmatic surface. Histopathologically, several non-caseous epithelioid cell granulomas and silicotic nodule-like lesions of hyaline degeneration were found; therefore, pneumoconiosis, or more specifically chronic berylliosis, was suspected. Despite these symptoms, the patient did not have a history of exposure, and the results of the lymphocyte stimulation test using beryllium were negative in blood and bronchoalveolar lavage fluid. The patient was given a diagnosis of pleural sarcoidosis and has been observed without treatment.

[A case of spontaneous resolution of sarcoidosis with primary pulmonary cavitations].

On routine physical checkup, a 27-year-old man with productive cough was found to have multiple nodules with cavitation in the bilateral lung fields and mediastinal and hilar lymph adenopathy on chest X-ray film and CT scan. Serum levels of angiotensin converting enzyme and lysozyme were high. Tuberculin reaction was negative. Non-caseous epitheloid granulomas were confirmed in the bronchial wall specimens obtained by trans-bronchial biopsy. The number of lymphocytes and the CD4/CD8 ratio of lymphocytes in bronchoalveolar lavage fluid was increased. Therefore, pulmonary sarcoidosis was diagnosed, and the lung nodules with cavitation were considered due to sarcoidosis. The walls of the cavitations gradually thinned and had almost completely vanished after 6 months of careful observation without steroid therapy.

[Modifications of the cytoimmunological pattern of bronchoalveolar lavage (BAL) material caused by cigarette smoking in selected lower air-way diseases].

In the last years we have used flow cytometry as an auxiliary diagnostic tool in alveolar lymphocyte (i.e. originating from BAL) phenotyping in more than 500 persons suspected for lower airways pathology. In the study we compared the results of 1) BAL lymphocyte typing by flow cytometry, 2) cytological examination, respectively, in nonsmoking/smoking (NS/S) patients with lung sarcoidosis, n = 56/31, extrinsic allergic alveolitis (EAA), n = 9/5, silicosis, n = 15/18, idiopathic pulmonary fibrosis (IPF), n = 20/7, and pulmonary tuberculosis (TBC), n = 7/6. The results were related to the volume of BAL fluid recovery (higher value reflects the dominance of lower airways content versus bronchial content). In smoking patients, in comparison with respective NS, significantly higher total BAL cell numer (except TBC), higher macrophage percentage, lower lymphocyte percentage and lower CD4/CD8 ratio (except EAA) was found. CD4/CD8 results: 8.26 +/- 0.52 (NS) vs 4.29 +/- 0.65 (S) in sarcoidosis (p < 0.001), 1.18 +/- 0.44 (NS) vs 0.99 +/- 0.43 (S) in IPF (p < 0.05), 1.79 +/- 0.22 (NS) vs 0.73 +/- 0.11 (S) in silicosis (p < 0.001) and 1.64 +/- 0.57 vs 0.88 +/- 0.1 in TBC (p < 0.05). Additionally, cigarette smoking modified BAL pattern: 1. in sarcoidosis and silicosis lower CD4+ cell and higher CD8+ cell percentage; 2. in IPF increase in neutrophil percentage; 3. in TBC higher neutrophil and eosinophil percentage. Both in NS and S, BAL fluid recovery rate is significantly positively correlated with CD4/CD8 ratio and total BAL CD3+ cell number and negatively with BAL CD8+ cell percentage. Interpreting of BAL material cytoimmunology pattern should take into account data on cigarette smoking and BAL fluid recovery rate. The results obtained in the study may reflect more severe disease course in IPF and TBC.

Bilateral hilar lymphadenopathy

Bilateral hilar lymphadenopathy is a bilateral enlargement of the lymph nodes of pulmonary hila. It is a radiographic term for the enlargement of mediastinal lymph nodes and is most commonly identified by a chest x-ray. Causes The following are causes of BHL: Sarcoidosis Infection Tuberculosis Fungal infection Mycoplasma Intestinal Lipodystrophy (Whipple's disease) Malignancy Lymphoma Carcinoma Mediastinal tumors Inorganic dust disease Silicosis Berylliosis Extrinsic allergic alveolitis Such as bird fancier's lung Less common causes also exist: Eosinophilic granulomatosis with polyangiitis Human immunodeficiency virus Extrinsic allergic alveolitis Adult-onset Still's disease References Medical signs

[A case of pulmonary sarcoidosis with CD8 positive cell dominant alveolitis].

A 55-year-old woman was admitted for examination of bilateral hilar lymphadenopathy. Serum angiotensin converting enzyme was not elevated, but gallium-scan revealed an increased uptake in both lung hilus. The percentage of lymphocytes in the bronchoalveolar lavage fluid (BALF) was elevated (28.9%), and the proportion of OKIa1 positive cells was also elevated (50.5%). However, the ratio of cluster differentiation (CD) 4/8 was inverted at 0.5. Microscopic examination of the mediastinal lymph nodes revealed epithelioid cell granulomas without ceasation, and a diagnosis of sarcoidosis was made. Immunohistochemical examination of the lymph nodes showed predominancy of CD8 positive cells. Patients with pulmonary sarcoidosis having a low CD4/8 ratio in BALF are extremely rare in the early stage of sarcoidosis. The inverted CD4/8 ratio was of interest in regard to the pathogenesis of sarcoidosis.

CD8+ cell-dominant alveolitis in pulmonary sarcoidosis.

A 55-year-old woman had bilateral hilar lymphadenopathy and retinouveitis. Microscopic examination of a biopsy specimen from a mediastinal lymph node revealed noncaseating epithelioid cell granulomas. Since granulomatous diseases of infectious origin and sarcoid reaction were reasonably excluded, she was diagnosed as having pulmonary sarcoidosis. Bronchoalveolar lavage findings were atypical in that the ratio of helper T cells to suppressor T cells (CD4/8 ratio) was 0.5 in two separate examinations, despite a moderately increased proportion of lymphocytes. Immunohistochemical examination of the lymph node also showed a predominancy of suppressor T cells. The inversion of the CD4/8 ratio suggests the presence of heterogeneity in the immunoregulatory mechanism in pulmonary sarcoidosis and may have a prognostic significance.

[Transbronchial biopsy in diffuse infiltrative lung diseases].

224 transbronchial biopsies were made between 1990 and 1997 in 208 patients suffering diffuse, bilateral, disseminated pulmonary diseases with unidentified origin. The examinations were carried out by flexible bronchoscope with X-ray control after local anaesthesia. The obtained patterns yielded mucous membrane in 15, intact alveoli in 19 percent. In 25 percent of biopsies (57 cases) definitive diagnosis were verifiable. The histological examinations verified the diagnosis of sarcoidosis, hemosiderosis, TB, malignancies, eosinophil pneumonitis etc. In 71 biopsies (62 cases) according to histological opinion were pulmonary fibrosis or some synonyms of these (alveolitis, interstitial fibrosis). From these latter cases the documentation of 18 patients were insufficient, but the data of 44 cases were available. 7/44 carcinosis, 3/44 inactive TB, 8/44 regressive X-ray patterns were verifiable in this group. The idiopathic pulmonary fibrosis as final diagnosis only in 18/44 (41%) cases were established. Further diagnostic procedures are needed if the clinical data, the results of HRCT and histological examinations are not in correlation.

[A study of epithelioid cell granulomas in transbronchial lung biopsy specimens of sarcoidosis patients--correlation between granulomas and clinical activity or chest X-ray lesions].

The 565 pulmonary tissue specimens taken from 155 sarcoidosis patients by transbronchial lung biopsy (TBLB) were studied by light microscopy. Particular attention was paid to the mean number and type of epithelioid cell granulomas, the mean number of giant cells, and the degree of lymphocyte cuffing, perigranulomal fibrosis, and granuloma confluence. The granulomas were divided into three types, hypertrophic, atrophic, and hyalinofibrous. In stage II and III patients, the mean number of granulomas and giant cells, the positive rate of hyalinofibrous granuloma, the relative proportion of the hyalinofibrous granuloma group, and the degree of fibrosis and confluence were significantly higher than those in stage O and I patients. The mean number of granulomas was related to the serum level of angiotensin converting enzyme and 67Ga uptake into lung parenchyma, but not to the cellular findings of bronchoalveolar lavage fluid (BALF). The lymphocyte count of BALF in the hypertrophic granuloma group was significantly higher than that in the atrophic and hyalinofibrous granuloma groups. CD4/CD8 ratio of lymphocytes in BALF was significantly lower in the hyalinofibrous granuloma group than in the other groups. In stage I patients, the resolution of intrathoracic lesions on chest X-ray was significantly more frequent in the atrophic granuloma group than in the hypertrophic granuloma group, 2 and 5 years after TBLB was performed. The pulmonary lesions had a tendency to persist for a long time in stage II and III patients with hyalinofibrous granuloma or granuloma confluence. Newly appearing pulmonary lesions showed hypertrophic granulomas as well as marked lymphocyte cuffing.

Bronchoalveolar lavage cell profiles in Wegener's granulomatosis.

Pulmonary involvement due to Wegener's granulomatosis (WG) can present radiologically either as diffuse infiltrates or as nodular and linear opacities. Clinical experience suggest that these radiological patterns are associated with different bronchoalveolar lavage (BAL) cell profiles, but this has not been examined formally. We compared the BAL cell profile in eight WG patients with diffuse infiltrates on chest X-ray, indicative of highly active pneumonitis, with corresponding findings in 37 patients with nodular, linear and focal low-attenuation infiltrates on high-resolution computed tomography (HRCT) which reflected low-grade, mainly interstitial disease. A control group was composed of 11 patients with pulmonary sarcoidosis. Diffuse infiltrates occurred in association with high systemic disease activity and featured a neutrophilic BAL profile in the presence of generally normal BAL lymphocytes. HRCT findings suggestive mainly of interstitial disease were associated with either a lymphocytic BAL cell profile or a normal cell pattern. Patients with a lymphocytic cell profile generally had a preferential elevation of CD4+ cells in the BAL in the presence of a normal CD4/CD8 ratio in the blood. This was a common feature of WG and pulmonary sarcoidosis. In conclusion, highly active pneumonitis and pulmonary disease of low or moderate activity in WG are associated with disparate BAL cell profiles. It remains to be examined whether the preferential elevation of CD4+ cells in the latter condition reflects a common pathogenetic role of this subset of cells in WG and pulmonary sarcoidosis.

Relationship between radiologic patterns, pulmonary function values and bronchoalveolar lavage fluid cells in newly diagnosed sarcoidosis.

The aim of the present study was to identify specious radiologic and/or physiologic prognostic marker(s), which lead to optimize of the patient follow-up frequency. Eighty consecutive patients with newly diagnosed pulmonary sarcoidosis. Patients underwent chest radiography, high-resolution computed tomography (HRCT) examination, pulmonary function tests (PFT), bronchoscopy with bronchoalveolar lavage (BAL) and lung biopsy, and bronchoalveolar lavage fluid (BALF) cell examination. The reduction in PFT values seen in radiological sarcoidosis stage III was greater than that seen in stages I and II. The percentage of neutrophils in the lungs was found to increase in stages II and III. PFT indices were correlated negatively with the consolidation and ground glass opacities CT scores, but not with the micronodule or macronodule scores. The rise in the percentage of BALF lymphocytes was associated with the restriction pattern of PFT. The diagnostic value of BALF for sarcoidosis was higher when the typical radiologic patterns of stage I disease were found and that smoking decreased the diagnostic value of CD4/CD8 ratio. This study supports the opinion that the staging of the pulmonary sarcoidosis with chest X-rays is still valuable from the prognostic point of view, because significant correlations between the radiologic stages of sarcoidosis and PFT parameters were found. Chest HRCT was significantly superior to chest X-ray in detecting mediastinal and pulmonary parenchymal changes. However, the prognostic role of HRCT needs to be better investigated evaluating serial examinations. Only consolidation and ground glass scores (neither of which are frequently found in sarcoidosis) hold prognostic value, since these were negatively correlated with PFT parameters.

[A case of subacute necrotizing lymphadenitis with localized interstitial pneumonia].

A 16-year-old male was admitted with a history of cervical lymph node swelling, high fever, cough and hemosputum. On admission, bilateral cervical lymph nodes swelling and fine crackles in the right lower lung field were noted. A chest X-ray film showed an infiltrative shadow in the right lower lung field and right hilar enlargement. Cervical lymph node biopsy specimens revealed wide areas of necrosis with nuclear debris. Transbronchial lung biopsy showed infiltration of lymphocytes in the interstitium and bronchoalveolar lavage fluid showed increased T-lymphocytes and a decreased T4/T8 ratio. The patient was diagnosed to have subacute necrotizing lymphadenitis with T-lymphocyte alveolitis. Additionally, antinuclear antibodies were positive, and anti HTLV-I antibody was false positive. These findings suggested an immunological abnormality in this case. His cervical lymph node swelling and infiltrative shadow on chest X-ray film improved with steroid therapy. Our case may be the first case of subacute necrotizing lymphadenitis with T-lymphocyte alveolitis.

Bronchoalveolar lavage in interstitial lung diseases: does the recovery rate affect the results?

Bronchoalveolar lavage (BAL) is an established diagnostic tool in interstitial lung diseases. BAL frequently yields findings of diagnostic value and at times even confirmatory diagnostic results. The present study has been designed to investigate whether the recovery rate affects BAL results relative to the instilled volume. Six hundred and eighteen patients with the following diagnoses were included into the study: 236 with sarcoidosis, 85 with idiopathic pulmonary fibrosis, 83 with cryptogenic organizing pneumonitis, 64 with connective tissue disease affecting the lungs, 54 with respiratory bronchiolitis with interstitial lung disease, 51 with extrinsic allergic alveolitis and 45 control patients. BAL was performed during flexible bronchoscopy with an irrigation volume of 100 ml 0.9% saline solution in 5 aliquots of 20 ml each. Only patients with a recovery of at least 30 ml were evaluated. Initially, the entire patient population was analysed, followed by an analysis within the different diagnostic groups and a comparison between patients with a high (>50 ml) and low (< or =50 ml) recovery rate. The recovery rate varied between the diagnostic groups (p < 0.001) and was negatively correlated with age (r = -0.21, p < 0.001) and smoking history (r = -0.11, p < 0.035). There were no correlations with inspiratory vital capacity (%pred.; p = 0.26) and forced expiratory volume in 1 s (%pred.; p = 0.15), but a positive correlation with the index (forced expiratory volume in 1 s/inspiratory vital capacity) x 100 (r = 0.23, p < 0.001). The cellular and non-cellular constituents of BAL were not affected by the recovery: cells/millilitre BAL (p = 0.71), relative proportion of macrophages (p = 0.92), lymphocytes (0 = 0.33), neutrophils (p = 0.14) and eosinophils (p = 0.11), albumin concentration (p = 0.13), and proportion of albumin in total protein (p = 0.06). The same applied for the lymphocyte surface markers CD4 (p = 0.72) and CD8 (p = 0.53). In the group with a high recovery rate, patients with sarcoidosis had a lower proportion of eosinophils (p = 0.04) and patients with cryptogenic organizing pneumonitis a higher concentration of albumin (p = 0.02) and lymphocytes (p = 0.007). Otherwise, no further differences were detected. The recovery rate hardly affected the cellular and non-cellular constituents of BAL at a lower limit of 30% of the instilled volume.

Chest radiograph

Pleural effusions may occur with cancer, sarcoid, connective tissue diseases and lymphangioleiomyomatosis. The presence of a pleural effusion argues against pneumocystis pneumonia. Reticular (linear) pattern (sometimes called "reticulonodular" because of the appearance of nodules at the intersection of the lines, even though there are no true nodules present) idiopathic pulmonary fibrosis connective tissue disease sarcoidosis radiation fibrosis asbestosis lymphangitis carcinomatosa PCP Nodular pattern sarcoidosis silicosis/pneumoconiosis extrinsic allergic alveolitis Langerhans cell histiocytosis lymphangitis carcinomatosa miliary tuberculosis metastases Cystic cryptogenic fibrosing alveolitis (late stage "honeycomb lung") cystic bronchiectasis Langerhans cell histiocytosis lymphangioleiomyomatosis Ground glass extrinsic allergic alveolitis desquamative interstitial pneumonia alveolar proteinosis infant respiratory distress syndrome (RDS)

InternalMed_Harrison

FIGURE 310-2 Open-lung biopsy from a patient with subacute hypersensitivity pneumonitis demonstrating a loose, nonnecrotiz-ing granuloma made up of histiocytes and multinucleated giant cells. Peribronchial inflammatory infiltrate made up of lymphocytes and plasma cells is also seen. (Courtesy of TJ Gross; with permission.) Bronchoscopy Bronchoscopy with bronchoalveolar lavage (BAL) may be used in the evaluation of HP. Although not a specific finding, BAL lymphocytosis is characteristic of HP. However, in active smokers, a lower threshold should be used to establish BAL lymphocytosis, because smoking will result in lower lymphocyte percentages. Most cases of HP have a CD4+/CD8+ lymphocyte ratio of less than 1, but again, this is not a specific finding and has limited utility in the diagnosis of HP.

Sarcoidosis

Serum markers of sarcoidosis, include: serum amyloid A, soluble interleukin-2 receptor, lysozyme, angiotensin converting enzyme, and the glycoprotein KL-6. Angiotensin-converting enzyme blood levels are used in the monitoring of sarcoidosis. A bronchoalveolar lavage can show an elevated (of at least 3.5) CD4/CD8 T cell ratio, which is indicative (but not proof) of pulmonary sarcoidosis. In at least one study the induced sputum ratio of CD4/CD8 and level of TNF was correlated to those in the lavage fluid. A sarcoidosis-like lung disease called granulomatous–lymphocytic interstitial lung disease can be seen in patients with common variable immunodeficiency (CVID) and therefore serum antibody levels should be measured to exclude CVID.

Influence of age on manifestation, VC and TLCO values, and bronchoalveolar lavage cell counts of sarcoidosis and extrinsic allergic alveolitis.

Immune response probably changes during human life, being influenced by cumulative exposure to environmental factors and individual genetic background. Patients investigated for suspected interstitial lung disease were prospectively enrolled. After completing the diagnostic process, 121 patients were diagnosed extrinsic allergic alveolitis (EAA) and 136 sarcoidosis. Three groups according to age were established (<30 years, 30-60 years, >60 years), clinical manifestation, vital capacity (VC), forced expired volume in 1 s (FEV1 ), lung diffusing capacity for carbon monoxide-transfer factor (TLCO ) and bronchoalveolar lavage fluid (BALF) differential cell count were compared among the groups. Age subgroups of EAA patients did not significantly differ in lung functions. In the group above 60 years, non-significantly higher neutrophils and eosinophils counts and CD4/CD8 ratio were observed. Sarcoidosis patients were significantly younger than EAA group and had significantly better lung functions (VC, FEV1 , TLCO ). Patients with sarcoidosis above 60 years of age had significantly higher percentages of neutrophils in BALF compared with younger patients. BALF percentage of neutrophils positively correlated with age. Presented results may support the hypothesis that reactivity of immune system changes during the life, which may result in different manifestation of interstitial lung diseases according to age.

[Flow cytometry for extensive thoracic diagnosis].

Immunophenotyping of cells by flow cytometry has become a routine test to diagnose pulmonary and mediastinal diseases. Peripheral blood, extravascular fluids, bronchoalveolar lavage (BAL) and suspension of single cells obtained by fine-needle aspiration can be used. Peripheral blood (MOAb for immunophenotyping of lymphocytes: CD14, CD45, CD3, CD19, CD4, CD8, CD16/56, HLA DR, CD38, CD25) is the material of choice for detection and monitoring of immunodeficiences. BAL (MOAb for immunophenotyping of lymphocytes: CD14, CD45, CD3, CD19, CD4, CD8, CD16/56, HLA DR) is used mainly for differential diagnosis of extrinsic allergic alveolitis (low CD4/CD8 ratio) and sarcoidosis (high CD4/CD8 ratio). The enumeration of alveolar macrophage subsets is an important tool to establish diagnosis of histiocytosis X (CD1a > 3%). Extravascular fluids, suspension of single cells and BAL are preferred materials for detection and classification of non-Hodgkin lymphomas (MOAb for immunophenotyping of lymphocytes: CD14, CD45, CD3, CD19, CD4, CD8, CD16/56, HLA DR, CD38, CD25, CD23, CD5, CDl1c, CD30, light chain immunoglobulins).

[Diagnostic values of BAL and TBLB in patients with interstitial lung diseases].

In order to evaluate the diagnostic values of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) in interstitial lung diseases, we made a retrospective study of a total of 43 patients all of whom underwent examinations for both conditions at the same time. In the BAL examination, fractional analyses of cell differential counts were applied to the first 30 ml lavage (FBAL-I, bronchial lavage) and to the following 50 ml aliquot of the second and third lavages (FBAL-II and -III, the latter supposedly alveolar lavage) lavages respectively. This technique revealed the unique characteristics of bronchial and alveolar inflammations in a separate data and this is assumed to be a precise reflection of the pathogenesis of interstitial lung diseases. The evaluation values (EV) were graded from 1 to 5 for both results according to the following diagnostic significance: EV1: not useful, EV2: normal or only slight changes from normal level, EV3: moderate changes although not diagnostic, EV4: quite compatible findings for diagnosis and EV5: definitely diagnostic. The 19 patients (43%) whose EV in TBLB were either 4 or 5 were diagnosed as having sarcoidosis (3), hypersensitivity pneumonitis (1), tuberculosis (2), pneumoconiosis (6), histiocytosis X (3), pulmonary infiltration with eosinophilia syndrome (PIE) (1), collagen vascular diseases (1), panbronchiolitis (1) or lymphagiomyomatosis (1). Thirteen of them had a BAL EV 4 which consisted of rather characteristic patterns of cell differential counts: thus their diagnoses were reconfirmed. In the other 4 patients with hypersensitivity pneumonitis, tuberculosis or PIE, the diagnoses were established by the findings of BAL EV 4 although the EV of TBLB were 3 or 2. These results indicate that BAL alone hardly establishes a diagnosis but it can support the TBLB findings and increase a diagnostic ability by 10% in total. Basophilic leukocytes, mast cells and Langerhans cells in BAL were rather non-specific, but the former two frequently appeared in allergic states and the latter two were often present in fibrotic lungs. Histiocytosis X is indicated if Langerhans cells are recovered from more than a small percentage of the total cell counts.

[Pathologic diagnosis and clinical analysis of chronic extrinsic allergic alveolitis].

To study the clinicopathologic features and diagnostic approach of chronic extrinsic allergic alveolitis (EAA). Seven cases of chronic EAA diagnosed by open lung biopsy or lung transplant were enrolled into the study. The clinical and pathologic features were analyzed and the literature was reviewed. There were altogether 4 men and 3 women. The age of the patients ranged from 30 to 65 years (mean = 48 years). All cases represented chronic form and five cases diagnosed by open lung biopsy also showed features of recent aggravation, leading to hospitalization. Four cases had known history of exposure to inciting gases, pollens and pets, and only 2 cases were positive for allergens. High-resolution CT scan showed ground-glass attenuation and reticular pattern that often had a patchy distribution and central predominance. Bronchoalveolar lavage analysis showed marked lymphocytosis, with CD4(+)/CD8(+) ratio less than 1. Lung function test demonstrated a restrictive ventilatory defect, with decreased compliance, reduced diffusion capacity and high airway obstruction. Five cases had open lung biopsy performed and two cases had undergone lung transplantation. Pathologic examination showed bronchiolocentric cellular interstitial pneumonia, interstitial fibrosis, non-caseating epithelioid granulomas, epithelioid histiocytic infiltrate in the respiratory bronchioles and intraluminal budding fibrosis. The five cases with open lung biopsy performed also showed neutrophilic infiltrate in the alveoli. The two lung transplant cases were complicated by severe fibrotic changes. Chronic EAA demonstrates characteristic pathologic features. Definitive diagnosis requires correlation with clinical and radiologic findings due to possible morphologic mimicry of other diffuse parenchymal lung diseases.

InternalMed_Harrison

Sarcoidosis Lymphocytosis; CD4:CD8 ratio >3.5 most specific of diagnosis Organizing pneumonia Foamy macrophages; mixed pattern of increased cells characteristic; decreased CD4:CD8 ratio Diffuse alveolar bleeding Hemosiderin-laden macrophages, red blood cells Diffuse alveolar damage, Atypical hyperplastic type II pneumocytes drug toxicity Opportunistic infections Pneumocystis carinii, fungi, cytomegalovirustransformed cells Lymphangitic carcinomatosis, Malignant cells alveolar cell carcinoma, pulmonary lymphoma Alveolar proteinosis Milky effluent, foamy macrophages and lipoproteinaceous intraalveolar material (periodic acid–Schiff stain–positive) Pulmonary Langerhans cell Increased CD1+ Langerhans cells, electron histiocytosis microscopy demonstrating Birbeck granule in lavaged macrophage (expensive and difficult to perform) Asbestos-related pulmonary Dust particles, ferruginous bodies disease Berylliosis Positive lymphocyte transformation test to beryllium

[Pulmonary sarcoidosis -- clinical and bronchoscopic findings in relation to the radiographic stage].

The classification of pulmonary involvement in sarcoidosis is based upon the radiographic stage of disease. We investigated 170 patients with new detected sarcoidosis (stage I / II / III: 79 / 39 / 52) for differences between the stages in demographic data, lung function values and results of BAL. With a multinomial logistic regression model to estimate probabilities, we found an increased probability for stage I with lower age (p < 0.001), higher IVC and FEV1 (p < 0.001), a less intensive smoking history (p<0.035), in BAL with a lower count of eosinophils (p < 0.014), mast cells (p < 0.004), CD8 lymphocytes (p < 0.015) and a less content of alkaline phosphatase (p < 0.004). For stage III the opposite results apply. With higher cell counts in BAL the probability of stage II increased, of stage III decreased (p < 0.013). The most relevant diagnostic BAL parameter in sarcoidosis, i.e. the count of lymphocytes and CD4 cells, was not different between the radiographic stages. Between patients with different radiographic stages of sarcoidosis there are differences in demographic data, lung function values and the pattern of alveolitis.

Relationships between radiographic change, pulmonary function, and bronchoalveolar lavage fluid lymphocytes in farmer's lung disease.

Ninety four dairy farmers were investigated by chest radiography, pulmonary function tests, and bronchoalveolar lavage. They were divided into five groups--1: 11 subjects with acute farmer's lung; 2: 25 subjects with previously diagnosed farmer's lung who had stayed on their farm; 3: 15 farmers with previously diagnosed farmer's lung who had left the farm; 4: 23 precipitin positive symptomless farmers; 5: 20 precipitin negative symptomless farmers. The study evaluated the relationships between radiographic changes measured with a scoring system derived from the International Labour Office (ILO) classification, the results of pulmonary function tests, and bronchoalveolar lavage fluid. Thirty eight subjects had radiographic evidence of interstitial pulmonary infiltrates. Group 1 had the highest percentage of lymphocytes recovered by bronchoalveolar lavage (mean 66.3 (SD 19.2]. For all subjects carbon monoxide transfer factor (TLCO) and total lung capacity were negatively correlated with radiographic changes (r = -0.45 and -0.30; p less than 0.001 and less than 0.01 respectively). TLCO was also negatively correlated with radiographic change in group 2 (r = -0.59, p less than 0.005). The percentage of lavage lymphocytes was correlated with radiographic changes for all subjects (r = 0.36, p less than 0.001), but this correlation was not seen within groups. This study shows good correlation between radiographic abnormalities, pulmonary function changes and the cellular composition of bronchoalveolar lavage fluid.

InternalMed_Harrison

Chest radiography can rule out infection and other causes of pulmonary involvement, but compared to HRCT, it is relatively insensitive for detection of early ILD. HRCT shows subpleural reticular linear opacities and ground-glass opacifications, predominantly in the lower lobes, even in asymptomatic patients (Fig. 382-8). Additional HRCT findings include mediastinal lymphadenopathy, pulmonary nodules, traction bronchiectasis, and uncommonly, honeycomb changes. The extent of pulmonary interstitial changes on HRCT is a predictor of mortality in SSc. Bronchoalveolar lavage (BAL) can demonstrate inflammation in the lower respiratory tract and may be useful for ruling out infection. Although an elevated proportion of neutrophils (>2%) and/or eosinophils (>3%) in the BAL fluid is correlated with more extensive lung disease on HRCT and is associated with more rapid decline in FVC and reduced survival, BAL is not useful for identifying reversible alveolitis. Lung biopsy is indicated only in

[Cytological examination of bronchoalveolar lavage fluid and its clinical significance in patients with diffuse interstitial lung diseases].

Cytological examination of bronchoalveolar lavage fluid (BALF) was carried out in 48 patients with diffuse interstitial lung diseases based on chest roentgenography. 7 cases manifested with respiratory symptoms but without any abnormality on both chest roentgenogram and fibroptic bronchoscopy served as controls. The total cell counts of BALF in the study group were all higher than those of the control group (3.1 x 10(5)/ml) and the differential count of the cells showed that neutrophilic granulocytes was found in patients with fibrosing alveolitis, Neutrophilic granulocytes accounted for 21.3 +/- 2.4% of all the cells and the percentage was significantly higher than that of the control group (1.8 +/- 0.5% P less than 0.01). On the contrary, lymphocytosis was found in patients with allergic alveolitis and sarcoidosis; lymphocytes accounted for 30.8 +/- 5.3% and 29.0 +/- 1.1% of all the cells in these two diseases respectively and the percentage was also higher than that of the control group (3.0 +/- 0.6% P less than 0.01). However, the differential cell count of BALF in alveolar carcinoma showed no significant difference with that of the control group (P greater than 0.05). The factors influencing the quality control of both BAL and cytological examination were evaluated and the clinical significance of these results was discussed.

Clinical usefulness of bronchoalveolar lavage cellular analysis and lymphocyte subsets in diffuse interstitial lung diseases.

Diffuse interstitial lung diseases (DILDs) form a part of a heterogeneous group of respiratory diseases. Bronchoalveolar lavage (BAL) analysis has been used for differential diagnosis of DILDs, but their clinical usefulness is controversial. The aim of this study was to investigate the clinical usefulness of BAL cellular analysis with lymphocyte subsets for the differential diagnosis of DILDs. A total of 69 patients diagnosed with DILDs were enrolled. Basic demographic data, BAL cellular analysis with lymphocyte subsets, histology, and high resolution computed tomogram (HRCT) findings were analyzed and compared as per disease subgroup. Significant differences were found between groups in the proportion of neutrophils (P=0.0178), eosinophils (P=0.0003), T cells (P=0.0305), CD4 cells (P=0.0002), CD8 cells (P<0.0001), and CD4/CD8 ratio (P<0.0001). These findings were characteristic features of eosinophilic pneumonia and sarcoidosis. Other parameters were not significantly different between groups. At the cut-off value of 2.16 for sarcoidosis, CD4/CD8 ratio showed sensitivity of 91.7% (95% CI, 61.5-98.6%) and specificity of 84.2% (95% CI, 72.1-92.5%). Routine analysis of BAL lymphocyte subset may not provide any additional benefit for differential diagnosis of DILDs, except for conditions where BAL is specifically indicated, such as eosinophilic pneumonia or sarcoidosis.

[Bronchoalveolar lavage findings in patients with diffuse interstitial lung disease: prospective study of a cohort of 562 patients].

Study of the bronchoalveolar lavage (BAL) fluid in some interstitial lung diseases can reveal patterns typical to each disease and that can support the diagnosis. The objective of this study was to perform a descriptive analysis of the cytologic study and of the lymphocyte subpopulations in BAL fluid from patients with interstitial lung disease. In this prospective, observational study of 562 patients between January 1991 and January 2005, BAL fluid was analyzed to determine the distribution of cell populations and of lymphocyte subsets: CD3, CD4, CD8, CD3(+)CD4(-)CD8(-), and CD56. The mean age was 53.4 years and 53.3% of the patients were women. The following diseases were studied: idiopathic pulmonary fibrosis (n=132), sarcoidosis (n=123), connective tissue diseases (n=133), cryptogenic organizing pneumonia (n=89), and extrinsic allergic alveolitis (n=85). Isolated lymphocytic alveolitis was common in sarcoidosis and extrinsic allergic alveolitis. Mixed alveolitis was the most common pattern in the other interstitial lung diseases. The CD4:CD8 ratio was the most useful parameter. It was high in sarcoidosis (median, 2.3); the ratio was low or inverted in the other interstitial lung diseases, with median values of 1.76 in idiopathic pulmonary fibrosis, 0.45 in extrinsic allergic alveolitis, 0.35 in cryptogenic organizing pneumonia, and 0.33 in the connective tissue diseases. BAL parameters, in association with clinical and radiologic data, help to discriminate between interstitial lung diseases. BAL should therefore be considered a very useful tool in clinical management, particularly when pulmonary biopsy is not conclusive or is not possible.

Persistent bronchoalveolar lymphocytosis in asymptomatic farmers.

We previously demonstrated that 14 of 23 asymptomatic dairy farmers with positive precipitins and 5 of 20 without precipitins had an alveolar lymphocytosis (greater than 22%). To verify the outcome of this lymphocytosis, we restudied, 2 or 3 yr later, 27 of these subjects. No subject had had symptoms suggestive of farmer's lung disease either prior to the initial study or between the 2 studies. All were still on their farm. Physical examination and chest roentgenograms were normal for all subjects at both studies. Pulmonary function tests showed a small but significant change in RV (101.8 +/- 20.4% to 118.7 +/- 27.6% of predicted, p less than 0.05) and FVC (98.0 +/- 12.6% to 94.3 +/-9.5%, p less than 0.05), whereas TLC, FEV1, and DLCO showed no changes. Lymphocytes from BAL were still increased in 9 of 12 subjects, whereas 3 had returned to normal; of the 15 subjects with previous normal values, 3 now had an abnormal lavage lymphocytosis. There was no correlation between lung function variations and the percentage of lymphocytes in the previous or the present BAL. We conclude that a bronchoalveolar lymphocytosis is a persistent phenomenon in a large number of asymptomatic dairy farmers, and that this finding is not related to significant disease, at least in the time span studied.

[Value of bronchoalveolar lavage and findings of cytologic studies in the diagnosis of interstitial lung diseases].

In 27 patients with roentgenologically suspected interstitial pulmonary disease, bronchoscopy was carried out with the rigid bronchoscope. The examination material obtained (BAL fluid, transbronchial lung biopsy, perbronchial lymph node biopsy, mucosal biopsy) was submitted to a histological and cytological work-up. The established cell distribution in the BAL fluid confirmed the findings reported in the literature. In sarcoidosis, irrespective of the roentgenological stage, a 30 to 35% lymphocytosis was observed. The combination of BAL, perbronchial lymph node biopsy, transbronchial lung biopsy and bronchial mucosal biopsy permitted confirmation of the sarcoidosis in more than 90% of the cases. The -hit rate- of the perbronchial lymph node biopsy was 90.6% in stage 1, 85% in stage 2, and 77% in stage 3.

[A case of bucillamine-induced interstitial pneumonia].

Bucillamine [N-(2-mercapto-2-methylpropionyl)-L-cysteine] is an anti-rheumatic drug which was developed in Japan. Interstitial pneumonia induced by bucillamine has been reported in two patients with rheumatoid arthritis. In this report, we describe another patient who developed bucillamine-induced interstitial pneumonia. In August 1990, a 53-year-old man was admitted because of fever, dry cough and dyspnea on exertion (DOE). Five months previously, he had noted polyarthritis, and treatment with bucillamine was started in May 1990. His polyarthritis improved about 2.5 months after starting bucillamine, but he developed fever, dry cough, and DOE in August 1990. Chest X-ray on admission showed diffuse acinar and interstitial shadows predominantly in the bilateral upper lung fields. Pulmonary function tests revealed decreased vital capacity and diffusing capacity. Arterial blood gas (ABG) analysis revealed moderate hypoxemia with PaO2 67 Torr. After stopping bucillamine, the fever, dry cough, and DOE improved gradually, and the abnormal shadows on chest X-ray and ABG analysis showed moderate improvements. Bronchoalveolar lavage studies showed that total cell counts and proportion of lymphocytes were increased, and CD4+/CD8+ ratio of T cell subsets was decreased to 0.56. Transbronchial lung biopsy specimen revealed lymphocytic alveolitis and mild interstitial thickening. Lymphocyte stimulation test to bucillamine was negative, but patch test with bucillamine was positive. From the patient's clinical course, laboratory data, and pathologic findings, we concluded that this is a case of bucillamine-induced interstitial pneumonia. After treatment with corticosteroid, his chest X-ray and pulmonary function test showed marked improvements.(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of bronchoalvoeolar lavage in the diagnosis of lung disease].

Bronchoalveolar lavage (BAL) is an important tool for evaluating interstitial lung diseases. It provides information on inflammatory cells which play an important role in the pathogenesis of such diseases and complements the information of the lung biopsy. The method is based on the observation, that the cells recovered by BAL reflect the population of cells in pulmonary parenchyma. In healthy subjects the main cells in the lavage fluid are macrophages (> or = 80%), lymphocytes (10-20%), some few neutrophils (< or = 4%), eosinophils (< or = 3%) and single mast cells. There are significant differences in the distribution of cell types in never-smokers, exsmokers and current smokers. Generally the increase in the number of lymphocytes is a hallmark of granulomatous and allergic lung diseases. Evaluation of the lymphocyte surface antigen phenotypos allows the recognition of sarcoidosis (increased proportion of T-helper lymphozytes) and extrinsic allergic alveolitis (increased proportion of T-suppressor lymphocytes). High neutrophil counts are characteristic of fibrosing processes or of occupational diseases caused by inhalation of inorganic dust. The evaluation of the diagnostic accuracy of the BAL is difficult because the final diagnosis of many symptomatically cured patients is not clear. Nevertheless, the evaluation of our cases showed a surprisingly high overall diagnostic accuracy (> 80%). However, the accuracy of negative diagnosis (exclusion of a certain disease) is slightly higher than this of the positive ones (diagnosis confirmed).

Bird fancier's lung

Biochemistry Biochemical results tend to be difficult to pinpoint to BFL, but can support a diagnosis. BFL causes high concentrations of antibodies targeted against avian proteins, although this may also be found in people exposed to avian protein without the disease. These can be detected in a blood test. An inverted CD4+/CD8+ ratio is associated with lymphocytosis. Radiology X-ray or CT scans usually show physical changes to the lung structure (a "ground glass" appearance or a "mosaic" pattern) as the disease progresses. Mediastinal lymphadenopathy and bronchiectasis may also be seen. Precise distribution and types of tissue damage differ among similar diseases, as does response to treatment with prednisone. Up to 12% of x-rays may show no damage, whilst only 2% of CT scans show no damage.