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[Diagnosis of interstitial lung disease (ILD) in patients with systemic sclerosis. The significance of broncho-alveolar lavage (BAL) --personal observations].

Review of current literature on pathogenesis and diagnostic approach to interstitial lung disease (ILD) in systemic sclerosis (SSc) was presented. The review focused in particular on the bronchoalveolar lavage (BAL). The experimental study was aimed to established whether early performed BAL is corresponding with clinical data, especially within a group with signs and symptoms of overt ILD. BAL was performed in 25 non-smoking subjects (22 women, 3 men) with SSc (according to ARA) with no systemic steroids. Diagnosis of lung involvement (presented in 18 patients) was based on history and physical examination, chest X-ray, lung function tests and arterial blood gas determination. BAL was routinely stained and assessed. Changes in BAL cytological examination were observed in all patients. An increased total cell number as well as increased percentage of neutrophils and eosinophils was noted. A lymphocyte number rise was not statistically significant. A lung involvement in group with ILD was more advanced than in group without ILD and controls, i.e. neutrophilic alveolitis in half cases (9/18 vs. 0/7 in group with no ILD) and oesinophilic alveolitis in 33% cases (6/18 vs. 2/7). Lymphocytic alveolitis was found in one patient with ILD and in two patients without ILD. The value of BAL in a diagnostic approach to the ILD in SSc was emphasized. Sensitivity of BAL in case of early ILD seems to be comparable with sensitivity of lung function tests (e.g. DLCO) and computerized tomography. The answer to the question which of the above mentioned methods in most appropriate to detect ILD risk in SSc remains unknown.

Blood Gas Analysis↗

Fibroblast mitogens in bronchoalveolar lavage (BAL) fluid from asbestos-exposed subjects with and without clinical evidence of asbestosis: no evidence for the role of PDGF, TNF-alpha, IGF-1, or IL-1 beta.

Asbestosis is a fibrotic lung disease resulting from inhalation of asbestos fibres. Its pathogenesis is poorly understood but probably involves stimulation of fibroblast proliferation and collagen production by mediators released from inflammatory and resident lung cells. In vitro studies have implicate PDGF, TNF-alpha, IGF-1, TGF-beta, and IL-1 in asbestosis, but the role of these mediators in vivo is not known. This study aimed to characterize mediators in bronchoalveolar lavage (BAL) fluid from patients exposed to asbestos with (n = 24) or without (n = 34) asbestosis, compared with ten normal subjects. Human lung fibroblasts were exposed to serial dilutions of BAL fluids and the effects on fibroblast proliferation were assessed. The median mitogenic activity of BAL fluid from asbestos-exposed (17 per cent above medium control, range 3-44 per cent) and asbestosis (14 per cent, range 2-60 per cent) groups was higher than that of BAL fluid from controls (10 per cent, range 2-20 per cent; P < 0.01 and P < 0.05, respectively), but there was no significant difference between the patient groups. The mitogenic activity of BAL fluids was not reduced by incubation with neutralizing antibodies to PDGF-AA, PDGF-AB, PDGF-BB, TNF-alpha, IGF-1, and IL-1 beta. We conclude that BAL fluids from patients exposed to asbestos contain mitogens for human lung fibroblasts, but that PDGF, TNF-alpha, IGF-1, or IL-1 beta do not contribute to this activity.

Adult↗

Self-presentation of beryllium by BAL CD4+ T cells: T cell-T cell interactions and their potential role in chronic beryllium disease.

Chronic beryllium disease (CBD) is characterized pathologically by granulomatous inflammation in the lung, composed of a large core of epithelioid cells surrounded by a dense shell of CD4+ T cells. Using beryllium-specific CD4+ T cell lines derived from the bronchoalveolar lavage (BAL) fluid of CBD patients, we show that purified CD4+ T cells produced significant amounts of IFN-gamma and TNF-alpha upon exposure to beryllium in the absence of antigen-presenting cells (APC). However, unlike BAL T cells stimulated by beryllium in the presence of APC, self-presentation by BAL T cells did not induce detectable IL-2 production, and in its absence these activated T cells die from programmed cell death. Resting BAL CD4+ T cells constitutively express high levels of HLA-DP, lymphocyte function-associated antigen 1 (LFA-1) and ICAM-3. When stimulated with beryllium/APC, the adhesion molecule ICAM-1 was up-regulated, as well as several costimulation molecules including CD28, OX-40 (CD134), 4-1-BB (CD137) and B7-1 (CD80). Notably, CD28 was not up-regulated during self-presentation by BAL T cells, and these cells do not express OX-40L, suggesting that lack of appropriate costimulation was responsible for programmed cell death observed upon beryllium self-presentation. Restricting anti-MHC class II mAb completely eliminated beryllium-induced T cell proliferation during self-presentation and significantly reduced IFN-gamma and TNF-alpha production. Our data demonstrate for the first time that self-presentation by BAL T cells in response to beryllium can occur ex vivo, in the absence of professional APC, with a specific dependence on T cell-expressed MHC class II molecules and exogenous IL-2 for survival.

Antigen Presentation↗

DNA concentrations in BAL fluid of cystic fibrosis patients with early lung disease: influence of treatment with dornase alpha.

Recombinant DNase (dornase alpha) was shown to improve lung function and reduce pulmonary exacerbations in cystic fibrosis (CF) patients, but its effects on DNA concentrations in the lower airways remain unclear at the present time. As part of the Bronchoalveolar Lavage in the Evaluation of Anti-Inflammatory Treatment (BEAT) Study, a multicenter open study to evaluate the evolution of inflammation in CF patients with early lung disease and its modulation by dornase alpha treatment, we studied DNA concentrations in the bronchoalveolar lavage (BAL) fluid of 48 CF patients with mild lung disease. After the initial BAL, 29 patients received daily treatment with 2.5 mg of dornase alpha; 19 patients served as controls. BAL was repeated after 18 months in all patients. Mean BAL fluid DNA concentrations were not different between groups at baseline (mean +/- SD, 14.1 +/- 6.9 microg/ml for controls, and 17.6 +/- 11.2 microg/ml for the dornase alpha group), but higher than previously reported for infants with CF. A weak but positive correlation (P <0.01) was observed between the percentage of neutrophils in BAL fluid and DNA levels. On reassessment after 18 months, the percentage of neutrophils was not different between the two groups, but DNA had increased in controls, whereas decreased levels were observed in treated patients (P <0.03, t-test). DNA concentrations increased by more than 10 microg/ml in 7 of 19 controls compared to 2 of 29 CF patients treated with rhDNase (P=0.01, Fisher's test). Therefore, treatment with dornase alpha over 18 months reduces DNA load in BAL fluid, which may have a positive effect on the clearance of lower airway secretions.

Adolescent↗

Comparison of the effectiveness of 2,3-dimercaptopropanol (BAL) and meso-2,3-dimercaptosuccinic acid (DMSA) as protective agents against mercuric chloride-induced nephrotoxicity in rats.

The effectiveness of 2,3-dimercaptopropanol (BAL) and meso-2,3-dimercaptosuccinic acid (DMSA) on HgCl2-induced nephrotoxicity was studied in the rat. Seven groups of adult male rats were given a single sc toxic dose of HgCl2 (0.68 mg/kg) followed by 0.9% saline (positive control group), BAL (15, 30, and 60 mg/kg) or DMSA (50, 100, and 200 mg/kg) administered ip at 0, 24, 48, and 72 h thereafter. Although the renal function of HgCl2-exposed rats was slightly improved after BAL administration, Hg concentrations in the kidney were only reduced at 60 mg/kg. In addition, the protective effect of BAL was not dose-related. In contrast to BAL, DMSA was effective in increasing the urinary excretion of Hg and in reducing the renal Hg content. These results show that DMSA would be more effective than BAL in preventing or in protecting against inorganic Hg-induced nephrotoxicity.

Animals↗

Arsenic distribution in rabbits after Lewisite administration and treatment with British anti-Lewisite (BAL).

The standard treatment of Lewisite (dichloro(2-chlorovinyl)arsine) poisoning is by chelation with BAL (British anti-Lewisite, dimercaptopropanol). The present study investigated the effect of BAL treatment on the distribution of arsenic after Lewisite administration. Lewisite was administered subcutaneously at the LD10 and LD40 of the compound. Without BAL treatment arsenic was eliminated with a half-life in blood of between 55 and 75 hr and a blood clearance of 120 ml/hr/kg. Arsenic had a large volume of distribution of several liters per kilogram, indicating extensive distribution in tissues. The highest tissue concentrations, more than seven times blood concentrations, were found in the liver, lung, and kidneys. These organs maintained an approximately constant concentration ratio with blood during the sampling period. Concentrations in tissues with a blood-to-tissue barrier, such as the brain and the spinal cord, rose between 4 and 96 hr while blood concentrations declined more than fourfold over the same time period. BAL treatment by four equal, maximally tolerated doses over 12 hr substantially reduced arsenic concentrations in blood and tissues. For example, at 24 hr the concentrations in brain and liver (target organs for arsenic toxicity) were reduced by 65 to 89% over the range of Lewisite doses administered. The total exposure of brain and spinal cord was reduced by more than two-thirds by BAL treatment. Further, the blood clearance of arsenic was increased. BAL treatment enhanced the elimination of arsenic in two ways: by decreasing the tissue-to-blood partitioning which mobilizes arsenic into the blood stream, and by increasing the clearance of arsenic.

Adipose Tissue↗

BAL levels of interleukin-18 do not change before or during acute rejection in lungtransplant recipients.

STUDY OBJECTIVE: Acute rejection (AR) of the allograft is a major clinical problem after lungtransplantation. Repeated episodes of AR increase the risk of developing obliterative bronchiolitis, the main cause of mortality in this patient group. It is believed that AR is caused by T-lymphocytes reacting to donor antigens and in turn activating antigen presenting cells (APC) such as alveolar macrophages. Hypothetically, the interferon-gamma inducing cytokine IL-18 released from activated macrophages can play a role in the development of AR by modulating cytotoxic T-lymphocytes. DESIGN: To determine whether IL-18 may serve as a marker of AR, we retrospectively analysed the concentration of soluble IL-18 protein and inflammatory cells in bronchoalveolar lavage fluid (BAL) from lungtransplant recipients. PATIENTS: To minimize confounding factors, eight pairs of patients were matched for age, gender, pre-op diagnosis, type of operation, absence of infection and time post transplant. METHODS: BAL levels of IL-18 (ELISA) and BAL cell differentials were analysed before, during and after an episode of AR and compared with the matched control group. CONCLUSION: We found no changes in IL-18 concentration in BAL associated with AR. IL-18 in BAL did not correlate with BAL lymphocyte percentage. We conclude that change in soluble IL-18 protein does not constitute a useful marker of acute rejection in lung allograft recipients.

Acute Disease↗

Pulmonary infections diagnosed by BAL: a 12-year experience in 1066 immunocompromised patients.

Bronchoalveolar lavage (BAL) is a useful tool in the diagnosis of pulmonary infections in immunocompromised patients. We aimed to compare the spectrum of infectious pulmonary complications diagnosed using BAL in a large consecutive cohort of immunocompromised patients. The diagnostic yield of 1066 BAL specimens was analyzed in 4 different groups of immunocompromised patients (HIV; solid organ transplants; high-dose chemotherapy and/or stem cell transplants; other immunosuppressive therapy) suffering from fever, respiratory symptoms and/or infiltrates on chest X-ray. Specimens were analyzed for bacteria, mycobacteria, fungi, Pneumocystis jiroveci, cytomegalovirus (CMV) and other viruses. Two time periods were compared (1992-1996; 1997-2003). The overall diagnostic yield of BAL was 34% for bacteria, 22% for CMV, 15% for P. jiroveci, 6% for other viruses, 6% for mycobacteria and 2% for aspergillus. There were significant changes in the pattern of opportunistic infections between the 2 time periods. Mycobacterial infections decreased considerably in the HIV group (17.9 vs. 8.5%, P=0.02), while the incidence of P. jiroveci decreased mainly in the transplant group (32.6 vs. 7.9%, P<0.00001). This study demonstrates a changed pattern of pulmonary infections in immunocompromised patients diagnosed by BAL. The overall diagnostic yield of BAL remains high in immunocompromised patients with respiratory symptoms.

Bacterial Infections↗

[Quality and selection of samples of bronchoalveolar lavage (BAL) in diffuse pneumopathies].

Bronchoalveolar lavage (BAL) samples used to study immune or inflammatory response in interstitial lung disease must be representative of the lower respiratory tract. Thus, the selection of suitable samples must be part of routine practice. To assess the incidence of unsuitable BAL samples used for cytology and to determine the relation between parameters related to underlying disease and the quality of samples. One hundred sixty-one patients were enrolled. Seventy-two were HIV positive and had diffuse pulmonary infiltrates, 34 had idiopathic pulmonary fibrosis (IPF), 10 had sarcoidosis, 10 had hypersensitivity pneumonitis, 19 had interstitial lung disease and collagen diseases and 2 had pulmonary eosinophilia. Fourteen individuals formed the control group. The quality study was carried out by staining the BAL samples following a modified Wright-Giemsa technique and evaluating the samples by the selection criteria described by Chamberlain and colleagues (1987). We identified unsuitable samples from 53% of the HIV positive patients, from 35% of the IPF patients and from 21% of the interstitial lung disease patients with associated connective tissue disease. In the other groups, all samples were suitable for analysis. Intolerance of BAL with decreasing percentage of fluid recovered was significantly associated with sample quality, particularly in the IPF group. The cytology results that invalidated the samples differed by group. In all groups, unsuitable specimens had low cell counts. The finding or not of evidence of associated infection in HIV-infected patients, on the other hand, did not appear to determine sample quality in and of itself, although it did in samples related to other entities. We can predict that a high rate of unsuitable BAL samples will come mainly from patients with diffuse lung disease associated to HIV infection, IPF and interstitial lung disease with associated connective tissue disease. Tolerance to the technique influences quality of the specimen obtained and, therefore, should be taken into account in interpreting the findings of cytology. The criteria applied by the various teams using BAL should be unified, and it should be determined whether the exclusion of inappropriate samples affects the final composition of study groups.

Bronchoalveolar Lavage↗

Analysis of the T cell receptor Vgamma region gene repertoire in bronchoalveolar lavage (BAL) and peripheral blood of atopic asthmatics and healthy subjects.

We analyzed the T cell receptor (TCR) Vgamma repertoire in BAL and peripheral blood (PBL) of three mild stable atopic asthmatics and two non-asthmatic controls. We used the polymerase chain reaction (PCR) to establish the expression of the four Vgamma families, and to detect oligo or monoclonal expansion of gammadelta+ T cells, we resolved the PCR projects on denaturing and non-denaturing gels to find the extent of junctional diversity arising from differences in the lengths of the V(D)J junctions. We also subcloned and sequenced the PCR products to characterize fully the sequence diversity. BAL T lymphocytes from two asthmatic patients (treated with inhaled steroids) expressed only VgammaII and, in one of them, VgammaIIJgamma usage was restricted to JgammaP and JgammaP1 gene segments, contrasting with the VgammaJgamma repertoire found in his respective PBL. Analyses in denaturing and non-denaturing gels showed that the BAL VgammaIIJgammaP and VgammaIIJgammaP1 PCR products resolved into few bands, suggesting deletions at the juctions due to oligoclonal expansion. BAL T lymphocytes from the third asthmatic (not receiving inhaled steroids) expressed VgammaI, II and III, and the sequences of the in-frame TCR transcripts from this asthmatic and one healthy volunteer who expressed a similar BAL VgammaTCR repertoire showed clonal expansion of T cells expressing all three Vgamma families. Our analyses showed that much of the GammaDeltaT cell population found in BAL fluid of humans derives from clonally expanded T cells.

Adult↗

[Concentration of alkaline phosphatase (AP) and AP/albumin ratio in bronchoalveolar lavage (BAL) for the diagnosis of interstitial lung diseases].

As a result of several studies with different animal models there is evidence that the concentration of AP in BAL is produced in the pneumocyte II and that an increase of AP in the BAL is a marker of tissue damage. By measuring AP in the BAL of patients with interstitial lung diseases we investigated its potential role as a diagnostic tool. To detect plasma leakage we also measured the concentration of albumin in the BAL. We studied 85 patients with following diagnoses: Sarcoidosis in 34 patients (Stage 1/2/3 14/7/13), idiopathic pulmonary fibrosis (IPF) in 14, bronchiolitis obliterans with organizing pneumonia (BOOP) in 7, hypersensitivity pneumonitis (HP) in 6. The control group consisted in 24 patients (13 nonsmokers, 11 smokers). In IPF and BOOP we observed significantly higher concentrations of AP than in controls and sarcoidosis (42.4 +/- 36.6 and 35.6 +/- 16 vs. 15.8 +/- 12.7 and 15.0 +/- 9.8 U/l, p < 0.05, ANOVA). Compared with controls in sarcoidosis higher concentrations of albumin (5.7 +/- 4 vs. 13.2 +/- 10 mg/dl, p < 0.05, ANOVA) and a lower AP/albumin-ratio (3.6 +/- 3.0 vs. 1.3 +/- 0.9 U/10 mg, p < 0.05, ANOVA) were seen. This result is an argument against plasma leakage as the source of AP in BAL. There were no differences in AP and albumin between the different stages of sarcoidosis and between smokers and nonsmokers in the control group. We conclude, that there are different concentrations of AP and albumin in BAL in different interstitial lung diseases. Compared with controls we observed higher concentrations of AP and an AP/albumin-ratio in the normal range in IPF, a normal concentration of AP and a lowered AP/albumin-ratio in sarcoidosis.

Adult↗

BAL modulates glutamate transport in synaptosomes and synaptic vesicles from rat brain.

The therapeutic use of BAL (2,3-dimercaptopropanol) as treatment for poisoning has been halted by data suggesting serious neurotoxicity. This article is a report on the effects of BAL and other dithiols, DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercaptopropane-1-sulfonic acid), on [3H]glutamate release and uptake by rat brain synaptosomes and [3H]glutamate uptake by synaptic vesicles. BAL (100 microM) inhibited glutamate uptake (30%) and stimulated its basal release (30%) in synaptosomes, without affecting K+-stimulated release. BAL also inhibited glutamate uptake by synaptic vesicles (up to 60%). DMPS and DMSA (100 microM) had no significant effects on these parameters. The data reported here provide some evidence of glutamate involvement in BAL-induced neurotoxicity by demonstrating direct effects of BAL on glutamatergic system modulation.

Animals↗

Apoptosis resistant bronchoalveolar lavage (BAL) fluid lymphocytes in sarcoidosis.

BACKGROUND: Sarcoidosis is a chronic granulomatous lung disease of unknown origin. The accumulation of activated T cells at sites of inflammation represents an early stage in granuloma formation. Since mechanisms governing the normal resolution of inflammatory processes are poorly understood, this study aimed to investigate the apoptotic phenotype of peripheral blood and lung T lymphocytes from patients with sarcoidosis. METHODS: Bronchoalveolar lavage (BAL) was performed in 10 patients with active sarcoidosis and five healthy controls. RESULTS: Virtually no lymphocyte apoptosis, as determined by annexin V or Hoechst staining, was seen in either patients or controls. Sustained caspase-3 activity in non-apoptotic BAL fluid lymphocytes of the patients was detected, however, in agreement with in vitro studies demonstrating caspase activation after T cell receptor (TCR) triggering as a physiological response required for efficient T cell activation. Only 11.0% (range 7.7-17.6) of the BAL lymphocytes from sarcoidosis patients were annexin V positive after exposure to the apoptotic stimulus tributyltin compared with 55.0% (range 42.0-62.0) of BAL lymphocytes from healthy controls (p<0.001). After anti-Fas treatment only 8.5% (range 6-10) of BAL fluid lymphocytes from patients but 45.5% (range 38-62) from healthy controls were apoptotic. CONCLUSION: BAL fluid lymphocytes from patients with sarcoidosis display a non-apoptotic morphology associated with endogenous caspase-3 activity. They seem to be resistant to apoptosis, which might contribute to the accumulation of inflammatory cells in the lungs, persistence of inflammation, and the development and maintenance of granuloma.

Adult↗

The concentrations of five tumor markers in both BAL fractions in lung cancer patients in relation to cigarette smoking.

BACKGROUND: Lung cancer is the leading cause of death from cancer. Tobacco is related to the development of this type of tumor due to genetic alterations and to the secretion of certain biological markers. Bronchogenic carcinomas secrete a series of biological substances known as tumor markers. Some of these markers, such as carcinoembryonic antigen, neuron-specific enolase, tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and CYFRA 21.1, possess clear clinical value when analyzed in bronchoalveolar lavage (BAL) of patients with lung malignancies, particularly when they are analyzed in the two BAL fractions, bronchial (BF) and alveolar (AF), being more increased in the BF. For this reason, we intend to demonstrate that smokers with cancer secrete more biological substances in the BF and that the concentrations of these markers are higher in the BAL of smokers than in that of non-smokers. METHODS: The five aforementioned tumor markers were studied in the two BAL fractions of 52 lung cancer patients (46 smokers and 6 non-smokers). We performed BAL using 150 ml of 0.9% saline solution divided in three aliquots of 50 ml. The fluid obtained from the first 50 ml was the BF. The liquid from the other two aliquots was the AF. The five tumor marker concentrations were calculated in accord with the indications of the laboratory. RESULTS: The TPA and TPS levels in the BAL of lung cancer patients were more increased in the BF than in the AF, even when the patients were divided into smokers and non-smokers. When we compared smokers with non-smokers, the smokers had higher levels of TPS in the BF and of TPA in the AF. CONCLUSIONS: Thus, we believe that the cellular alterations produced by tobacco are responsible for the secretion of these tumor markers.

Aged↗

Are we ready to replace dimercaprol (BAL) as an arsenic antidote?

1 Dimercaprol (BAL), 2,3-dimercaptopropanesulphonate sodium (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are effective arsenic antidotes, but the question which one is preferable for optimal therapy of arsenic poisoning is still open to discussion. Major drawbacks of BAL include (a) its low therapeutic index, (b) its tendency to redistribute arsenic to brain and testes, for example, (c) the need for (painful) intramuscular injection and (d) its unpleasant odour. 2 The newer antidotes DMPS and DMSA feature low toxicity and high therapeutic index. They can be given orally or intravenously due to their high water solubility. While these advantages make it likely that DMPS and DMSA will replace BAL for the treatment of chronic arsenic poisoning, acute intoxication-especially with lipophilic organoarsenicals-may pose a problem for the hydrophilic antidotes, because their ionic nature can adversely affect intracellular availability. 3 This article focuses on aspects dealing with the power of BAL, DMPS, and DMSA to mobilize tissue-bound arsenic in various experimental models, such as monolayers of MDCK (= Madin-Darby canine kidney) cells from dog kidney, isolated perfused liver from guinea-pigs, and perfused jejunal segments from rat small intestine. 4 The results show that hydrophilic DMPS and DMSA may fail to rapidly and completely remove arsenic that has escaped from the extracellular space across tight epithelial barriers. However, owing to their low toxicity, which allows larger doses to be applied, and the potential modification of their pharmacokinetics by means of inert oral anion-exchange resins, DMPS and DMSA may advantageously replace BAL whenever intervention time is not critical. With severe intoxication by organic arsenicals, when the point-of-no-return is a limiting factor, BAL may still have a place as an arsenic antidote.

Animals↗

BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia.

Idiopathic pulmonary fibrosis (IPF), which has the histological pattern of usual interstitial pneumonia (UIP), is a progressive interstitial lung disease with a poor prognosis. Idiopathic interstitial pneumonias with a histological pattern of nonspecific interstitial pneumonia (NSIP) have a better prognosis than UIP, and may present with a clinical picture identical to IPF. The authors hypothesised that bronchoalveolar lavage (BAL) findings may distinguish between UIP and NSIP, and have prognostic value within disease subgroups. BAL findings were studied retrospectively in 54 patients with histologically proven (surgical biopsy) idiopathic UIP (n=35) or fibrotic NSIP (n=19), all presenting clinically as IPF. These findings were also compared with the BAL profile of patients with other categories of idiopathic interstitial pneumonias. BAL total and differential cell counts did not differ between the two groups. Survival was better in NSIP. In neither group were BAL findings predictive of survival or changes in lung function at 1 yr, even after adjustment for disease severity, smoking and treatment. BAL differential counts in fibrotic NSIP differed from respiratory bronchiolitis-associated interstitial lung disease, but not from desquamative interstitial pneumonia or cellular NSIP. The authors conclude that bronchoalveolar lavage findings do not discriminate between usual interstitial pneumonia and nonspecific interstitial pneumonia in patients presenting with clinical features of idiopathic pulmonary fibrosis, and have no prognostic value, once the distinction between the two has been made histologically.

Bronchoalveolar Lavage↗

[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.

Adolescent↗

BAL in children: a controlled study of differential cytology and cytokine expression profiles by alveolar cells in pediatric sarcoidosis.

STUDY OBJECTIVE: The development of BAL in children for both research and clinical purposes has been limited so far by the difficulty in establishing reference values. The aim of the study was (1) to define composition of BAL cellular components in control children and to evaluate the ability of these cells to express various cytokines, and (2) to study modifications of differential cytology and BAL cell cytokine responses in children with interstitial lung disorders. POPULATIONS AND METHODS: Two groups were investigated: a control group of 16 children who were concluded to be free of parenchymal lung disease after complete pulmonary investigation, and a group of 11 children with pulmonary sarcoidosis. Differential cytology was evaluated by standard techniques. BAL cell cytokine expression was studied at the level of messenger RNA (mRNA) by reverse transcription-polymerase chain reaction (RT-PCR) methods. RESULTS: In the control group, differential cell counts appeared to be similar to values reported in adult populations with normal distribution of the data and no influence of age. In this group, no transcripts for interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and transforming (correction of tranforming) growth factor-beta (TGF-beta) could be detected. In children with sarcoidosis, different profiles of IL-1beta, TNF-alpha, IL-6, and TGF-beta expression were individualized which seemed to be related to the activity and/or severity of the disease, IL-6 and TGF-beta mRNA being observed only in the more severe forms. CONCLUSION: These data provide information on BAL cell number and function in children. Characterization of BAL cytokine expression patterns during the course of interstitial lung diseases in children may be of great interest for evaluation of disease activity and/or severity and therefore for planning of therapy.

Actins↗