Lymphocytic alveolitis: A surprising index of poor prognosis in patients with primary Sjogren's syndrome.

Twelve years ago we reported that lymphocytic alveolitis [or bronchoalveolar lavage (BAL) lymphocytosis] correlates with clinical pulmonary involvement in primary Sjogren's syndrome (pSS). Our thesis was based on subtle clinical and functional evidence of interstitial lung disease (ILD) in pSS patients with "high lymphocytic alveolitis" (>15% lymphocytes in BAL). This report is a follow-up study of these patients. Basic clinical and functional re-evaluation of the 22 patients with pSS, studied in 1991, emphasized the differences between those with alveolitis and those without alveolitis. There was no significant functional decline. There were, however, two statistically significant differences between the two groups: (1) only patients with BAL lymphocytosis had to be treated with steroids (5/12 vs. 0/10, P < 0.05) and (2) only patients with BAL lymphocytosis had died in the mean time (6/12 vs. 0/10, P < 0.01). The causes of death were various. On only two occasions were they related to respiratory infections while there were no deaths from respiratory failure secondary to ILD. BAL lymphocytosis appears to be a surprisingly serious index of dismal prognosis in patients with pSS. We offer no unifying pathophysiologic mechanism for it and, therefore, all we propose is that BAL is performed early, in as many patients with pSS as possible. These patients should then be followed up systematically, in order to evaluate if BAL lymphocytosis has any pathophysiologic importance in the development of clinically serious pSS, which is serious enough to lead to death.

Gastrointestinal hormones and short-term nutritional schedules in critically ill patients.

BACKGROUND/AIMS: The purpose of the study is to evaluate the gastrointestinal hormone response in critically ill patients under different nutritional schedule (enteral vs. total parenteral) of short duration. METHODOLOGY: Twenty-one sedated and mechanically ventilated patients were nourished with continuous nasogastric schedule (Group A, 11 patients), or with total parenteral nutrition (Group B, 10 patients). Serum concentrations of gastrin, cholecystokinin, vasoactive intestinal peptide, neurotensin, and bombesin, were measured on the 2nd, 3rd and the 5th day of patients' admission, with radioimmunoassay methods. RESULTS: Changes of hormones concentrations were not significant either between the three measurements in each group or between the two groups at the same hospitalization day. CONCLUSIONS: The short-term parenteral nutrition in critically ill patients does not exert a different influence on the serum concentrations of gastrin, cholecystokinin, vasoactive intestinal peptide, neurotensin, and bombesin, compared to enteral nutrition. This conclusion is of clinical interest since the short-term administration of total parenteral nutrition is very often necessary during hospitalization in the intensive care unit.

Evaluation of the end-expiratory pressure by multiple linear regression and Fourier analysis in humans.

This study was designed to compare the end-expiratory pressure (EEP) during mechanical ventilation (MV) measured dynamically (EEPdyn), by multiple linear regression (MLR) of the airway pressure (Pao) vs volume (V) and flow (V') and after Fourier analysis (FA) of the Pao and V'. Pao and V' were recorded from 32 ICU patients (II without respiratory disease, 10 COPD, II ARDS) under MV, at three levels of PEEPe (0, 5 and 10 hPa). Volume was calculated by numerical integration of V'. Data were analysed by MLR and FA, while the actual value of EEPdyn was recognised on the Pao signal at zero V' and V. EEPdyn, EEPMLR and EEPFA were compared for all patients, for each group of patients and for every level of applied PEEPe. Despite the different evaluation of respiratory mechanics between MLR and FA, the EEP values were always not significantly different between the three applied methods (P > 0.05). A high degree of correlation was found between them, taken two at a time (r > 0.99, P < 0.001). Two non-invasive analytical methods for the evaluation of respiratory mechanics during MV, MLR and FA offer a reliable and clinically useful estimation of EEP during MV.

Liquid phase characteristics of bronchoalveolar lavage in primary Sjögren's syndrome.

We have previously reported that alveolitis correlates with clinical, roentgenologic, and functional parameters of pulmonary involvement in primary Sjögren's syndrome (1SS). In the present study, we analyzed the liquid phase characteristics of bronchoalveolar lavage (BAL) in the same 19 patients with 1SS. Our results show that patients with "high alveolitis" (group A, BAL lymphocytes > 15.2 percent) have increased values of total protein, albumin, IgA, and IgG and in their BAL fluid compared with patients with "low alveolitis" (group B) and control subjects. Also interleukin 2 (IL-2) was detected in more "high alveolitis" patients while IgM, IL-2R, and interferon gamma (IFN-gamma) were detected only in this group. There were no differences between the two groups in serum values of all above factors as well as in the presence of rheumatoid factor, extractable nuclear antibodies, and antinuclear antibodies. The increased values of immunoglobulins and cytokines in the BAL fluid of patients with intense alveolitis, in the absence of serum differences, speak for their local production and suggest activation of local immune mechanism.

Lymphocytic alveolitis and pleural calcifications in nonoccupational asbestos exposure. Protection against neoplasia?

Inhabitants of the Metsovo area in Northwest Greece (population, 4,000) have been exposed to asbestos through the use of whitewash containing tremolite. This has resulted in endemic pleural calcifications (PCs) and increased incidence of malignant pleural mesothelioma (MPM). In order to evaluate the lung response to the fiber, bronchoalveolar lavage (BAL) was performed in 25 Metsovites; 14 with PCs, three with PCs and neoplasia, five without PCs, and three without PCs but with established neoplasia. There were no differences between the four groups with regard to age or exposure. Twelve Metsovites had lymphocytic alveolitis (BAL lymphocytes > 15%). Eleven belonged to the group with PCs and one belonged to the group without PCs. None of those with neoplasia had alveolitis. The lymphocytes were mainly helper T-cells, and activation markers were more frequent among those with PCs. We have previously reported on the relative absence of PCs in Metsovites with malignant pleural mesothelioma. This observation and the results of the present study suggest that lymphocytic alveolitis correlates with pleural calcifications, whereas both are rarely present in patients with neoplasia.

Alveolitis correlates with clinical pulmonary involvement in primary Sjögren's syndrome.

Bronchoalveolar lavage (BAL) was performed in 23 patients with primary Sjögren's syndrome (1Ss) and ten healthy controls to evaluate alveolitis and correlate it with pulmonary and systemic manifestations. Patients with 1Ss had higher BAL total cell count (9.2 +/- 6.7 millions/ml vs 6.1 +/- 2.9 millions/ml) and higher percentage of lymphocytes 23.3 +/- 15.6 percent vs 6.5 +/- 2.9 percent, p less than 0.001) than controls. Twelve patients (group A) constituted the "high alveolitis" group (lymphocytes greater than 15.2 percent) and ten (group B) constituted the "low alveolitis" group (lymphocytes less than 15.2 percent). Group A had more frequent cough (6/12 vs 2/10, p = 0.07), dyspnea (4/12 vs 1/10), and roentgenologic evidence of interstitial lung disease (5/12 vs 0/10, p less than 0.05). They also had lower total lung capacity (85.6 +/- 14.2 percent pred vs 105.8 +/- 23.3 percent pred, p less than 0.05) and Dco (87.7 +/- 20.6 percent pred vs 103.6 +/- 21.0 percent pred). All patients with +3 or +4 grading or lymphocytic infiltrates in lip biopsy specimen belonged in group A (5/12). Finally, T-helper/T-suppressor ratio was lower in group A than in group B. The intensity of alveolitis was not correlated with clinical or serologic manifestations of systemic disease.

Effect of cyclosporin A (CyA) on the immunopathological lesion of the labial minor salivary glands from patients with Sjögren's syndrome.

Labial minor salivary gland biopsy specimens from 14 patients with Sjögren's syndrome treated either with cyclosporin A (CyA) or placebo (5 mg/kg body weight day for six months) were studied to determine T lymphocyte subsets and HLA-DR antigen expression using the avidin-biotin-peroxidase technique. In all CyA treated patients we observed a decrease in the number of T lymphocytes and in the number of T helper cells, while the percentage of T suppressor cells and B cells was the same in both treated and untreated groups. It was also shown that the HLA-DR antigen expression on the epithelial cells was eliminated in the CyA treated patients. These findings suggest that the HLA-DR antigen expression on the epithelial cells is the result rather than the triggering factor of this T cell mediated process and is probably related to decreased lymphokine production by activated T lymphocytes.

HLA-DR expression by labial minor salivary gland tissues in Sjögren's syndrome.

Minor salivary gland biopsy specimens from patients with Sjögren's syndrome (primary and secondary) and from normal controls were examined with the four step biotin-avidin-immunoperoxidase assay. The composition of the infiltrating cells was similar in patients with both primary and secondary Sjögren's syndrome, consisting primarily of T lymphocytes with predominance of T helper/inducer cells. B lymphocytes (Leu-14) were approximately 20-35% of the infiltrating lymphocytes, while only a few OKM1 (monocytes/macrophages) cells and Leu-7+ (natural killer; NK) cells were observed. The majority of infiltrating lymphocytes expressed HLA-DR antigens. In the biopsy specimens of the controls there were no infiltrates; the scattered lymphocytes, however, were also predominantly T lymphocytes. Finally, the glandular epithelial cells (ducts and acini) were inappropriately expressing HLA-DR antigens, in contrast with controls where minimal HLA-DR expression was found.

Labial salivary gland immunopathology in Sjögren's syndrome.

The cellular composition of the salivary gland infiltrates in primary Sjögren's syndrome and the presence of lymphokines were evaluated using the Avidin-Biotin-Peroxidase technique in 10 biopsies from patients with Sjögren's syndrome. The 10 specimens were stained with monoclonal antibodies (MoAb) against T-lymphocytes (Leu-4), Monocytes/Macrophages (M phi) (Leu-M3 and OKM1), Natural Killer cells (NK) (Leu-11 and Leu-7), class II MHC antigens (anti HLA-DR and OKIa1, anti Leu-10), Interleukin-2 (anti IL-2), IL-2 Receptor (anti IL-2 receptor) and Interferon gamma (IFN-gamma) (supernatant fluid from hybridoma cell line producing MoAb to IFN-gamma). The predominant cell was the T-helper/inducer lymphocyte. T-helper/T-suppressor ratio ranged from 1/1 to 10/1. Only few M phi were observed while NK cells were rare. More than 50% (50-100%) of the infiltrating cells were HLA-DR positive while epithelial cells were positive from 40-90% in all but two cases in which the positivity was 10%. The infiltrating cells were also positive for Leu-10 antigen (40-95%) in contrast to the epithelial cells. Both infiltrating and epithelial cells were reacting with anti IL-2 MoAb in high percentages (50-100%), while none of the infiltrating cells expressed IL-2 receptor. Finally, 40-100% of the infiltrating cells were IFN-gamma positive. Our data indicate that the salivary gland lesion in Sjögren's syndrome, is the result of an immune process in which T-lymphocytes predominate producing lymphokines, while the epithelial cells by expressing class II MHC molecules, occupy an important part of the picture.

Subclinical manifestations of autoimmune rheumatic diseases in primary Raynaud's phenomenon.

Twenty-nine patients with primary Raynaud's phenomenon underwent functional (pulmonary functional studies and oesophageal manometry), histologic (minor salivary gland biopsy) and serologic (autoantibodies) evaluation for subclinical manifestations of autoimmune rheumatic disease (ARD). Seven (24%) has strong evidence and eight (27%) possible evidence of ARD. All patients with strong evidence of ARD had Raynaud's phenomenon with a duration of less than five years. This study suggests that such manifestations are frequent in patients wih primary Raynaud's phenomenon and can be detected with non-aggressive methods which should be used early in the course of their disease.

Respiratory involvement in autoimmune rheumatic diseases is frequent and easy to detect.

90 patients with various autoimmune rheumatic diseases were evaluated for respiratory system involvement with simple clinical, roentgenological and functional methods. Seventy-three % had at least one indication of respiratory system involvement. The most common clinical findings were history of pleurisy, dyspnea and dry cough. The most frequent roentgenological pictures were pleural effusion or thickening and diffuse interstitial lung disease. The main functional abnormality was restriction followed by small airway disease. The study suggests that respiratory involvement in autoimmune rheumatic diseases is frequent and easy to detect.