Biomedical subjects

M Laviolette

Publications and source records attributed to M Laviolette.

At least 73 records · Page 4Linked to original sources

PubMed1994

Airway inflammation in nonasthmatic subjects with chronic cough.

The physiopathology of chronic cough remains obscure. We evaluated the possibility that chronic cough in nonasthmatic subjects is associated with airway inflammation, and if this is so, what the relationship between this inflammation and the possible etiology of cough might be, as well as its response to inhaled steroids. Nineteen nonsmoking, nonasthmatic subjects referred for a persistent cough (mean: 3.8 yr) were evaluated and compared with 10 normal subjects. The evaluation included a respiratory questionnaire, a physical examination, allergy skin-prick tests, chest and sinus radiographs, esophageal pH monitoring, measurements of expiratory flows, methacholine and citric acid challenges, and flexible bronchoscopy for bronchoalveolar lavage (BAL) and bronchial biopsies. Fourteen subjects further accepted participation in a randomized, double-blind crossover trial of inhaled beclomethasone (500 micrograms four times daily) and a placebo for 1 mo each. Four groups of subjects were identified according to the presence of postnasal discharge (n = 4), gastroesophageal reflux (n = 6), both conditions (n = 5), or neither (n = 4). Subjects with chronic cough had an increased number of inflammatory cells in their bronchoalveolar lavage fluid (BALF), but there was no significant difference between the four subgroups of coughers. As compared with control subjects, the bronchial biopsies of subjects with chronic cough showed increased epithelial desquamation (p = 0.004) and inflammatory cells (p = 0.005), particularly mononuclear cells (p < 0.01), in addition to submucosal fibrosis, squamous-cell metaplasia, and loss of cilia. These findings were not significantly different between the different etiologic groups. In subjects with chronic cough, basement-membrane thickness was normal and not different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Airway inflammation after removal from the causal agent in occupational asthma due to high and low molecular weight agents.

In order to determine 1) the features of airway inflammation after removal from exposure to high (HMW) and low (LMW) molecular weight agents 2) if there are any differences in the pattern of inflammation induced by these two types of agents, we studied 18 subjects with a recently confirmed diagnosis of occupational asthma (OA) due to HMW (n = 11) and LMW (n = 7) agents. The duration of asthma symptoms varied from 2 to 108 months (mean 33 months), and withdrawal from exposure to the sensitizing agent from 3 to 24 weeks (mean 10 weeks). All subjects underwent measurements of expiratory flow rates, methacholine inhalation tests, and a flexible bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsies. Endoscopic findings were compared with a group of 10 normal subjects. At the time of the bronchoscopy, asthma symptoms were minimal in most subjects. Although 15/18 subjects had normal forced expiratory volume in one second (FEV1 > 80% pred), all subjects had increased airway responsiveness to methacholine (provocation concentration producing a 20% fall in FEV1 = 0.2-10.0 mg.ml-1). BAL analysis showed similar median percentages of the total number of cells and differentials in control subjects and those exposed to HMW and LMW agents. Bronchial biopsies showed that mean inflammatory cell count, both epithelial and sub-epithelial, was similarly raised in OA subjects exposed to either HMW or LMW agents, compared to controls, except for epithelial lymphocyte count. In contrast to the controls, bronchial biopsy of both groups with OA also showed other changes such as extensive epithelial desquamation, ciliary abnormalities of the epithelial cells, smooth muscle hyperplasia and subepithelial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Comparison of two modified techniques for purifying blood eosinophils.

As there is much heterogeneity in the morphology and function of blood eosinophils, comparison of their properties between groups of subjects requires recovering the majority of these cells. In two currently used techniques to isolate eosinophils, blood granulocytes are processed either on Percoll gradients after an incubation of granulocytes with 10(-8) M N-formyl-methionyl-leucyl-phenylalanine (fMLP) or on a magnetic cell sorter (MACS). In this study, these techniques were modified to increase the efficiency of eosinophil recovery. With the Percoll gradients, using 1.078 g/ml as the top gradient instead of 1.082 g/ml doubled the eosinophil recovery from 43 +/- 5.3% (mean +/- SEM) to 86.9 +/- 2.9%, without decreasing the purity (96.1 +/- 1.4% versus 96.2 +/- 0.9%). With a MACS, the neutrophils in granulocytes obtained on Ficoll-Paque (1.077 g/ml) instead of on Percoll gradient 1.082-1.094 g/ml, were tagged with anti-CD16 antibodies and eliminated by passing them through a magnetic field. When blood eosinophils of the same subjects were isolated using the two techniques, similar recovery and purity levels were obtained: Percoll gradients, 72.7 +/- 6.8% and 92.5 +/- 2.2%; MACS, 80.2 +/- 5.1% and 90.4 +/- 3.8%. Eosinophils isolated through the two techniques were also compared for their production of superoxide anion and leukotriene (LT) C4, with and without pre-incubation with cytokines interleukin-3, interleukin-5 and granulocyte-macrophage colony stimulating factor. The release of these products was similar between the two eosinophil preparations under all conditions tested except for interleukin-3 where eosinophils isolated with a MACS produced more LTC4. These results show that both techniques efficiently recover pure eosinophils. Furthermore, cell incubation with 10(-8) M fMLP did not enhance superoxide anion and LTC4 production nor modify the response to cytokines. The two modified techniques are therefore suitable for comparative studies of eosinophils from different groups of subjects.

Adult↗

PubMed1993

Influence of natural antigenic exposure on expiratory flows, methacholine responsiveness, and airway inflammation in mild allergic asthma.

BACKGROUND: This study looked at respiratory symptoms, peak expiratory flow rates (PEFRs), airway responsiveness to methacholine and inflammatory changes on bronchial biopsies, bronchial lavage (BL), and bronchoalveolar lavage (BAL) during natural antigenic exposure in nine subjects with pollen-sensitized seasonal asthma. METHODS: The subjects recorded daily symptoms of asthma, cough and rhinitis, and morning and evening PEFRs between January and September, during and out of the pollen exposure. Baseline forced expiratory volume in 1 second, forced vital capacity, and methacholine responsiveness were measured every 3 to 4 weeks. BAL, BL, and bronchial biopsies were performed in the pollen season at the initial increase of asthma symptoms and out of pollen exposure. RESULTS: At the time of bronchoscopy during the pollen season compared with out of season, asthmatic subjects had an increase in asthma symptom score (1.18 +/- 0.24/0.44 +/- 0.18, p < 0.05), a reduction of PEFR (407 +/- 23/442 +/- 20 L/min, p = 0.02), and a decrease in PC20 (1.15/1.48 mg/ml, p = 0.05). In asthmatic subjects, median BAL and BL cell counts and cell differentials during or out of antigenic exposure were similar, but BAL and BL eosinophils and metachromatic cells counts were always higher than in healthy subjects. In comparison with controls, biopsies obtained in asthmatic subjects showed airway lesions such as epithelial desquamation, squamous cell metaplasia, thickening of basal membrane, inflammatory cells (p < 0.05 for neutrophils), edema, and ciliary abnormalities. During pollen exposure, inflammatory signs increased, but this change was only significant for the extent of epithelial desquamation and neutrophil counts. No significant correlation was found between the intensity of airway inflammation and changes in airway responsiveness. CONCLUSIONS: In subjects with mild allergic asthma and pollen-induced asthma, seasonal antigenic exposure was associated with an increase in epithelial shedding and in the number of neutrophils on bronchial biopsies, suggesting a mild increase in baseline airway inflammation. However, these changes were not correlated with increases in airway responsiveness.

Adult↗

PubMed1993

Cyclosporin A increases the pulmonary eosinophilia induced by inhaled Aspergillus antigen in mice.

We evaluated the effects of anti-inflammatory drugs in a murine model of allergic bronchopulmonary aspergillosis (ABPA). Mice instilled with 100 micrograms of Aspergillus fumigatus antigen (intranasally, 3 days a week for 3 weeks) developed pulmonary lesions, characterized by a perivascular and peribronchial eosinophil infiltration, a bronchoalveolar lavage (BAL) eosinophilia, and elevated levels of total IgE, total IgG1 and A. fumigatus-specific IgG1. Under the same conditions, groups of mice receiving a daily dose of 2 mg/kg dexamethasone showed decreased numbers of eosinophils and total cells in BAL, had less numerous eosinophils in their pulmonary infiltrates, and had lower levels of serum and BAL fluid total IgE, total IgG1 and A. fumigatus-specific IgG1. Conversely, groups of mice pretreated with an immunosuppressive agent, cyclosporin A (CsA) at a dose of 50 mg/kg, three times per week, developed pulmonary lesions with enhanced lung eosinophilic influx and increased total IgE levels, both in serum and in BAL fluid. These findings show that dexamethasone potently prevents the murine immunopathologic response to A. fumigatus. The effect of CsA on this inflammatory response was paradoxical, insofar as it suggests an activation of the T helper 2 subset, which up-regulates eosinophil recruitment and IgE production.

Administration, Inhalation↗

PubMed1993

A study of monokine release and natural killer activity in the bronchoalveolar lavage of subjects with farmer's lung.

We examined the interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) releasability of alveolar macrophages and the natural killer (NK) cell activity in the bronchoalveolar lavage (BAL) cells of 11 patients with Farmer's lung at different stages of the disease. Although there were some variations in the levels of monokine release, macrophages of patients with acute disease secreted significantly higher spontaneous levels of TNF alpha than did a nonfarming control group (p = 0.0002). Conversely, TNF alpha release stimulated by bacterial lipopolysaccharide (LPS) was similar in patients with acute disease when compared with that in normal control subjects. IL-1 was also spontaneously secreted in significantly greater amounts by patients with acute Farmer's lung than by subjects in a control group (p = 0.0001). However, LPS-induced IL-1 release was significantly diminished in BAL macrophages from patients with acute manifestations of the disease when compared with that in control subjects (p = 0.001). Treating hypersensitivity pneumonitis with corticosteroids or by contact avoidance resulted in very significant decrease in spontaneous and LPS-stimulated IL-1 production by BAL macrophages (p = 0.0001 and p = 0.03, respectively), as well as in a decrease in spontaneous TNF alpha release that was also significant (p = 0.01). In addition, BAL cells of patients in the acute phase had a significant NK cell activity (mean +/- SEM of 18.33 +/- 2.65%). Treatment of these patients resulted in an increase in NK cell activity (mean of 40.17 +/- 7.86%), which was significantly different from values of patients with acute disease (p = 0.037).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1993

Farmer's lung. Long-term outcome and lack of predictive value of bronchoalveolar lavage fibrosing factors.

This study evaluates the long-term outcome of farmer's lung (FL), adding high-resolution computed tomograms (HRCT) to previously reported procedures and verifying whether bronchoalveolar lavage (BAL) fluid markers or substrates of fibrosis (hyaluronic acid, Type III procollagen, fibronectin, and fibroblast growth factors) (FF) predict outcome. A total of 33 subjects with a history of FL dating back at least 6 yr were evaluated with pulmonary function tests, chest x-ray (CXR), and HRCT. All subjects had an initial evaluation, which included a BAL, 6 yr before the current study. Subjects were then either in acute FL (n = 19) or in clinical remission despite continued contact (n = 14). In the current study, pulmonary function tests revealed an obstructive profile in 13 subjects, restrictive changes in 1, an isolated decrease in lung diffusion capacity in 3, and normal values in 16. Chest radiographs (CXR) were normal in 22 subjects, abnormal with interstitial or reticulonodular changes in 6, and suggestive of emphysema in 5. HRCT revealed emphysema in 9 subjects; 3 had localized fibrotic changes, 2 a ground-glass pattern, and 19 were normal. There was a good correlation between the findings on pulmonary function tests and HRCT; however, CXR alone did not suggest the existence of emphysema in 4 subjects who had such findings on HRCT. No correlations were found between most outcome parameters and the level of the BAL FF measured 6 yr previously. We conclude that airflow obstruction with or without emphysema is an important long-term sequela of FL and that BAL FF do not predict outcome in this disease.

Acute Disease↗

PubMed1993

Farmer's fever. Systemic manifestation of farmer's lung without lung involvement.

A 35-year-old dairy farmer presented with recurrent febrile episodes over more than three years. Fever up to 39 degrees C occurred only if he was in contact with the dairy barn and typically appeared at 4 to 8 h after an otherwise usual barn exposure. He had no dyspnea and throughout this period repeated physical examinations, chest roentgenograms, and lung functions remained normal. He was bronchoscoped and lavaged on three occasions, a lymphocytic alveolitis was always present and once, immediately after an acute episode, an important increase in lavage neutrophils was also found (47 percent). Transbronchial lung biopsy specimens showed a moderate cellular infiltrate but no granuloma or fibrosis. Three other persons who worked at the same farm had no similar manifestations or respiratory illnesses. The patient therefore had typical systemic manifestations of acute farmer's lung, but without the lung involvement required to confirm that diagnosis. Furthermore, his disease does not fit the entities known as grain fever and organic dust toxic syndrome. We believe that this patient presented a different entity that we coined "farmer's fever."

Adult↗

PubMed1993

Fibrogenic activities in bronchoalveolar lavage fluid of farmer's lung.

Hyaluronic acid (HA), type III procollagen, fibronectin, and fibroblast growth factors (FGF) were measured in 43 bronchoalveolar lavage fluid (BALF) specimens obtained from 38 patients with farmer's lung (FL) and in BALF of 9 nonexposed normal control subjects. Bronchoalveolar lavage was done in 21 farmers with acute FL (acute) and in 22 with a history of previous FL (Ex) who were still in daily contact with dairy barns. All farmers from the acute and Ex groups had a lymphocytic alveolitis, respectively, 62.7 (3.5) percent (mean [SEM]) and 48.1 (4.3) percent. Hyaluronic acid, type III procollagen, fibronectin, and FGF were all highly increased in acute disease. These substances were also increased in the BALF of subjects of the Ex group who had no clinical symptoms or signs of acute disease at the time of lavage, but were actively farming. The increase in type III procollagen, however, was less in this group than in the subjects with acute disease. These observations suggest that the fibrosing activities and potentialities of the allergic alveolitis of FL are fully expressed at the time of clinical presentation and also in the subclinical phase of the disease in susceptible farmers who remain exposed after an initial acute phase of the disease.

Adult↗

PubMed1992

Studies of the inhibitory activity of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)-indol- 2-yl]-2,2-dimethyl propanoic acid) on arachidonic acid metabolism in human phagocytes.

We have investigated the inhibitory activity of compound MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)-i ndol-2- yl]-2,2-dimethyl propanoic acid) on 5-lipoxygenase (5-LO) product synthesis in various human phagocytes stimulated with either the ionophore A23187, opsonized zymosan (OPZ), platelet-activating factor (PAF), or formyl-methionyl-leucyl-phenylalanine (fMLP). The lipoxygenase products were analyzed by reversed-phase HPLC. MK-0591 inhibited the formation of 5-hydroxyeicosatetraenoic acid, leukotriene (LT) B4, its omega-oxidation products, and 6-trans-isomers with IC50 values of 2.8-4.8 nM in A23187-stimulated neutrophils. In these conditions, arachidonic acid at a concentration of 10 microM had no effect on MK-0591 inhibitory activity. In neutrophils stimulated with OPZ, the synthesis of LTB4, its omega-oxidation products, and 6-trans-isomers was inhibited with IC50 values of 9.5-11.0 nM. MK-0591 inhibited 5-LO product synthesis in A23187-stimulated blood monocytes, eosinophils, and alveolar macrophages with IC50 values of 0.3-0.9, 3.7-5.3, and 8.5-17.3 nM, respectively. In neutrophils primed with granulocyte--macrophage colony-stimulating factor and stimulated with PAF, lipoxygenase product synthesis was inhibited with IC50 values of 7.7-8.7 nM. At the concentration of 1 microM, MK-0591 had no inhibitory effect on 15-lipoxygenase activity in human polymorphonuclear leukocytes, nor on human platelet 12-lipoxygenase and cyclooxygenase. In conclusion, MK-0591 is a very potent and specific inhibitor of 5-LO product synthesis in various types of human phagocytes.

Adult↗

PubMed1992

Murine hypersensitivity pneumonitis: a study of cellular infiltrates and cytokine production and its modulation by cyclosporin A.

The progression of hypersensitivity pneumonitis (HP) was evaluated in mice repeatedly challenged with the actinomycete Faeni rectivirgula (Micropolyspora faeni) (90 or 180 micrograms), at the cellular level and at the mediator level. Instillation of F. rectivirgula by the intranasal route determined a granulomatous inflammation in the lungs of animals correlated with a dramatic increase (5- to 6-fold) in cellularity in the bronchoalveolar space and an increase in the percentage of lymphocytes. Disease in mice was also correlated with high spontaneous release of the cytokines interleukin-1 (IL-1) (60 U/ml), interleukin-6 (IL-6) (72 U/ml), and tumor necrosis factor-alpha (TNF-alpha) (56 U/ml) in the bronchoalveolar lavage (BAL) fluid, as well as by an enhanced capacity for cytokine release by macrophages upon stimulation with F. rectivirgula. It was also found that the pulmonary inflammation was correlated with a 60 to 70% increase in total lung weight after 4 wk and a significant lung fibrosis as seen by a 2-fold increase in lung hydroxyproline levels. Treatment of challenged mice with cyclosporin A (CyA) led to an abrogation of the disease as seen by an abrogation of the increase in lung index, lack of IL-1 and TNF-alpha release in the BAL. CyA did not, however, completely prevent the alveolitis as seen by the cellular infiltrate (2- to 3-fold in BAL cell increase). It also did not prevent the T-lymphocyte recruitment associated with HP, although these cells did not proliferate in response to the F. rectivirgula antigen, in contrast to BAL cells from F. rectivirgula-challenged mice treated with excipient only.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMed1992

T cells in hypersensitivity pneumonitis: effects of in vivo depletion of T cells in a mouse model.

C57BL/6 mice were given intranasal instillation of optimal doses of the actinomycete Faeni rectivirgula 150 micrograms/mouse 3 days/wk), an important offending agent causing hypersensitivity pneumonitis. This instillation was associated with a very significant increase in the lung weight of the mice and also a large increase (10-fold) in the number of cells recovered from the bronchoalveolar lavage (BAL) of instilled mice. Also, this instillation was associated with a very significant fibrosis at 4 and 8 wk (2-fold increase in hydroxyproline levels in the lungs). We determined the effect of depleting certain T-cell subsets on the progression of this inflammatory disease. Elimination of the L3T4 subset did not significantly affect the increase in the lung index, the lung cellular influx, or its profile. Fibrosis was also unaffected by this depletion of L3T4+ cells. Similarly, depletion of Lyt2+ (CD8+) cells did not lead to significant changes in these disease parameters. Depletion of all T cells (Thyl+) was also ineffective at modifying the number of infiltrating cells and the lung index score. However, identification of cell types in BAL showed that mice depleted of Thyl+ cells had a cellular influx that was almost exclusively neutrophilic throughout the instillation period, whereas control mice developed only a transient neutrophilic response to F. rectivirgula instillation, which was replaced by a recruitment of mononuclear cells, mostly macrophages. Also, depletion of Thyl+ cells before and during F. rectivirgula challenge had no effect on tumor necrosis factor-alpha levels in the BAL of treated mice (63 +/- 13 U/ml in anti-Thy1. 2 antibodies treated versus 52 +/- 10 U/ml in the BAL of control mice given F. rectivirgula).(ABSTRACT TRUNCATED AT 250 WORDS)

Actinomycetales Infections↗

PubMed1992

Lymphocytic alveolitis and airway responsiveness in recently diagnosed sarcoidosis.

We looked at the relationship between the intensity of the lymphocytic alveolitis and airway responsiveness to methacholine, in patients with recently diagnosed untreated pulmonary sarcoidosis. We studied 19 subjects, 13 M and 6 F, aged 19-58 (mean: 36.6) who had a diagnosis of pulmonary sarcoidosis within the last 6 months (radiologic stages: I, 10 subjects; II, 8; III, 1). One subject had a previous history of asthma but was currently asymptomatic. Five were smokers, 5 ex-smokers and 9 non-smokers. Initial assessment included a flexible bronchoscopy with bronchoalveolar lavage (BAL), measurement of expiratory flows, lung volumes, CO diffusion and a methacholine inhalation test. Pulmonary function tests were repeated six months later, and a second evaluation of airway responsiveness to methacholine was obtained in 13 patients. Mean % of lymphocytes, neutrophils and macrophages on BAL were respectively: 25.4, 2.3 and 72.4. Mean % of predicted values for FVC, FEV1, FEF25-75%, TLC, FRC and DLCO were respectively 91.3, 94.3, 88.8, 97.6, 102.1 and 91.2. In all subjects FEV1 was > or = 80% and PC20 was in the normal range (> 16 mg/ml in all subjects but one who had a PC20 of 12.0). There was no correlation between the % of BAL lymphocytes and the initial PC20. At 6 months, overall airway responsiveness was unchanged (geometric mean initial/6 month PC20 methacholine: 95.9/102.8) whether or not the subjects had a high intensity alveolitis (defined as > or = 30% lymphocytes on BAL).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Influence of lung volume on collateral resistance in normal man.

We measured the influence of changing the end-expiratory lung volume (EELV) on collateral resistance (Rcoll) in 6 normal volunteers (5 male, 1 female, aged 23-45 years). With subjects lying supine in an iron lung, a 5.3 mm fibroscope was introduced under local anesthesia and wedged into a sub-segmental bronchus of the right lower lobe. A truncated 5f Swan-Ganz catheter was tightly fitted into the suction port of the fibroscope. One lumen of the catheter served to deliver a constant flow (200 ml/min) of 5% CO2 in air. The pressure in the wedged segment (Ps) was measured by the other channel. Airway pressure (used as alveolar pressure (Palv)) was determined with a low bias flow catheter taped to the side of the bronchoscope, its tip positioned 20 cm from the end of the bronchoscope. Rcoll was obtained by the formula: Rcoll = (Ps-Palv)/flow. EELV was passively changed by applying a constant extrathoracic pressure in the iron lung at 5 cm H2O steps from 0 to +15 and from 0 to -20 cm H2O. The changes obtained in Rcoll (% baseline, mean +/- SEM) at each extrathoracic pressure (ETP) were: -5 cm H2O, 73 +/- 4%; -10, 56 +/- 7%; -15, 56 +/- 9%; -20, 35 +/- 10%; +5, 118 +/- 6%; +10, 129 +/- 7%; +15, 118 +/- 11%. Rcoll progressively decreased with increasing EELV (negative ETP) and increased slightly as EELV was reduced (positive ETP). The relationship between the log Rcoll and delta EELV was linear; the slope of this line was 9.8%.

Adult↗

PubMed1991

Bronchoalveolar mast cells in normal farmers and subjects with farmer's lung. Diagnostic, prognostic, and physiologic significance.

To evaluate the specificity and significance of increased lavage mast cells in farmer's lung, we examined the lavage cell differentials of 89 farmers and 19 normal nonfarming control subjects. The farmers were divided into four groups: acute farmer's lung (n = 17), farmers with one or more prior episodes of farmer's lung who remained in daily contact with hay (n = 26) or quit farming (n = 14), and normal farmers (n = 36). A total of 14 of the subjects with prior episodes of farmer's lung and still farming and 15 normal farmers were evaluated twice at a 2-yr interval. The lavage mast cell numbers were significantly higher in acute farmer's lung (7.5 +/- 7.3 x 10(3)/ml, mean +/- SD) and ex-farmer's lung who were still farming (1.2 +/- 1.3 x 10(3)/ml) than in normal farmers (0.1 +/- 0.1 x 10(3)/ml) (p less than 0.01). A total of 8 of 14 exfarmer's lung patients who had quit farming and 18 of 36 normal farmers had an increased number of mast cells in lavage, but mast cell count never exceeded 0.5% of total recovered cells. In the acute farmer's lung and ex-farmer's lung-still farming groups, the mast cell count correlated with the lymphocyte count: r = 0.83 and r = 0.69 (p less than 0.001), respectively. In the two groups evaluated twice, mast cell numbers at the first study did not correlate with changes seen at the second study in chest roentgenogram and pulmonary functions. We conclude that an increase in lavage mast cells occurs commonly as a part of the immune response against thermophilic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1991

Hypersensitivity pneumonitis: whole Micropolyspora faeni or antigens thereof stimulate the release of proinflammatory cytokines from macrophages.

Hypersensitivity pneumonitis (HP) is an allergic granulomatous interstitial lung disease resulting from a reaction of selected individuals to repeated inhalations of certain antigens. HP is characterized by chronic inflammation, and the development of the disease seems to be immunologically mediated. In farmer's lung, the source of provoking antigen has been found to be actinomycetes such as Micropolyspora faeni. In this study, we show that M. faeni, or antigens thereof, stimulate strong release of proinflammatory cytokines from blood monocytes and alveolar macrophages obtained from nonfarmer volunteers and naive mouse peritoneal macrophages. Interleukin-1 (IL-1) was produced by human alveolar macrophages and murine peritoneal macrophages in response to whole M. faeni and antigens thereof. IL-1 activity was detected in the supernatants at 12 h of incubation and was maximal by 24 to 36 h (200 to 400 U/ml of IL-1). A rabbit antiserum to IL-1 alpha and IL-1 beta neutralized the thymocyte-stimulating activity of the supernatants. Moreover, M. faeni (1 to 100 micrograms of antigen) elicited a strong secretion of tumor necrosis factor-alpha (TNF-alpha) from human alveolar macrophages and monocytes as well as mouse peritoneal macrophages, where 1 micrograms of M. faeni elicited the secretion of approximately 100 U of TNF-alpha from 2 x 10(5) macrophages, and 100 micrograms stimulated the release of approximately 1,000 U of bioactive TNF-alpha. One particle of whole M. faeni per cell was sufficient to induce copious release of TNF-alpha from macrophages or monocytes (100 U of bioactive TNF-alpha; 1,000 pg/ml of antigenic TNF-alpha as seen by radioimmunoassay). Both IL-1 and TNF-alpha productions stimulated by M. faeni were not abrogated by inclusion of polymyxin B. We propose that the direct stimulation of cytokines by M. faeni or antigens thereof may play an important role in HP.

Alveolitis, Extrinsic Allergic↗

PubMed1991

Tumor necrosis factor plays an essential role in determining hypersensitivity pneumonitis in a mouse model.

We examined the importance of the cytokine tumor necrosis factor-alpha (TNF-alpha) in a mouse model of hypersensitivity pneumonitis (HP). Mice of the C57BL/6 strain were instilled intranasally 3 days/wk for 3 wk with 150 micrograms of the actinomycete Faenia rectivirgula (Micropolyspora faeni) to induce HP as a model of farmer's lung. This experimental model was associated with a progressive inflammation in the lungs of challenged mice, seen histologically as cellular infiltrates of large quantities of macrophages and lymphocytes and some neutrophils. The disease in challenged mice treated with a control rabbit serum was also associated with a substantial release of tumor TNF-alpha (up to 80 U/ml of TNF-alpha in the bronchoalveolar lavage [BAL] at 3 wk after beginning of treatment) and interleukin-1, which peaked at 1 wk (approximately 300 U/ml) and diminished thereafter. A very large increase in BAL cell number (11-fold increase versus saline controls) and an enhanced release potential for TNF-alpha by alveolar macrophages was also seen. Lung fibrosis was also evident in challenged animals, as demonstrated by a 2-fold increase in hydroxyproline levels. Infusion of challenged mice with a rabbit polyclonal antibody against TNF-alpha (2 mg/wk) completely abrogated the disease, as mice so treated had normal lung histology. Anti-TNF-alpha blocked cellular recruitment in the lungs (only a 2-fold increase at week 3); it also completely abolished TNF-alpha secretion in the BAL and drastically reduced interleukin-1 levels in this fluid. Anti-TNF-alpha also abolished lung index increases and lung fibrosis, with both parameters similar to that of saline-instilled mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗

PubMed1991

Prognostic value of bronchoalveolar lavage lymphocyte count in recently diagnosed pulmonary sarcoidosis.

We prospectively looked at the prognostic value of bronchoalveolar lavage (BAL) lymphocyte count in 98 patients with recently diagnosed (less than 4 months) untreated sarcoidosis. These 50 men and 48 women (mean age, 37.4) were followed up for a period of 6 to 60 months (mean, 25.6), and were clinically evaluated every three to six months with repeated chest roentgenograms and pulmonary function tests. Twenty-four patients required steroid treatment during the study period. The proportion of treated patients was not significantly higher in the group presenting a BAL lymphocyte count less than or equal to 30 percent at diagnosis than in the group with fewer lymphocytes (31.9 and 17.7 percent of total group respectively, p = 0.10). No significant change in TLC, FRC, FVC, FEV1 or DLCO was found at follow-up between the groups with or without an initial high lymphocyte count. In the treated group, BAL lymphocyte percent weakly correlated with the improvement of FEV1 and FVC while on steroid treatment (mean duration: 3.5 months): r = 0.41, p = 0.031 and r = 0.36, p = 0.05 respectively; no correlation was found with lung volumes and DCO. We conclude that BAL lymphocyte count at the time of diagnosis is not a helpful predictor of lung function deterioration in recently diagnosed sarcoidosis and is not very useful in predicting response to treatment.

Adult↗