Longstanding endobronchial foreign body.

There are many circumstances in which the diagnosis of endobronchial inhalation of a foreign body (FB) can be missed. Generally, in such cases, within weeks or at most months from the event, clinical bronchopulmonary symptoms develop which allow a correct diagnosis to be made and significant complications to be avoided. We report the case of a patient in whom an endobronchial FB remained undiagnosed, because of lack of symptoms, for almost three years, and then caused signifiicant complications before being identified and removed. Problems related to diagnosis and therapy are discussed.

Serum type I and type III procollagen peptide levels in sarcoidosis.

Type I and type III are the most abundant collagens in the lung. The aim of our study was to compare type I and III procollagen peptides in sera of sarcoid patients. Sixty eight patients with sarcoidosis were studied (19 with newly recognized disease, 7 with relapsing disease, 15 with chronic disease, and 27 in stable remission). Thirty healthy volunteers served as controls. The levels of procollagen I and III peptides were determined by radioimmunoassay. Angiotensin-converting enzyme (ACE) level was evaluated by means of a colorimetric assay. In patients with newly recognized sarcoidosis, both serum procollagen I and III peptide levels were increased with respect to controls (p=0.0014 and p<0.00001, respectively). There was a poor correlation between levels of procollagen I and III (r=0.26), whereas there was a closer correlation between procollagen III and ACE (r=0.69). Procollagen I peptide level did not identify patients in roentgenological stage III. In conclusion, in patients with newly recognized sarcoidosis there is a significant increase in the serum level of procollagen I peptide. However, procollagen I peptide is not a marker of sarcoid patients with fibrosis, ie. stage III disease. Its clinical usefulness seems to be weaker than that of procollagen III peptide.

"The sarcoidosis map": a joint survey of clinical and immunogenetic findings in two European countries.

We pooled immunogenetic data obtained in independent studies in two European populations (Italian and Czech) of patients affected by sarcoidosis. Correspondence analysis was used to investigate the associations between clinical and immunogenetic data. Two hundred and thirty-three patients were enrolled in the study, of which 126 were from the Czech Republic and 107 from Italy. Using a common protocol, we examined each patient for sex, age of disease onset, roentgenologic stage, extrapulmonary spread, and clinical course. One thousand and ten healthy individuals, HLA typed for class I and II serologic polymorphisms, served as controls. Findings that were essentially in agreement in both populations were: (1) a positive association of sarcoidosis with HLA-A1, B8, and DR3 markers, and a negative association with HLA-B12 and DR4; (2) a prevalence of HLA-DR3 and DR4 among females and of DR5 among males; (3) a relationship of B13 and B35 with early onset and of A30, B8, DR3, and DR4 with late onset of disease; (4) an association of B27 with sarcoidosis restricted to the lungs; (5) a relationship of A1, B8, B27, and DR3 to roentgenologic stage I and of B12 and DR4 to stage III; and (6) an association of HLA-DR3 with a good outcome. Population-restricted findings essentially concerned the alleles HLA-B13 and B22, the former being associated with the disease, male sex, early onset, extrapulmonary localization and relapse only in Czechs, and the latter to disease spread only in Italians. Our results seem to support the concept that immunogenetic background may at least partly account for the clinical heterogeneity of sarcoidosis.

HLA class I, II, and III polymorphism in Italian patients with sarcoidosis. The Pavia-Padova Sarcoidosis Study Group.

We studied the HLA polymorphisms (class I, II, and III) in 107 Italian patients with biopsy specimen-proven sarcoidosis in order to investigate the immunogenetic background of this disease. The mean age of onset of the disease was 36.08 +/- 12.4 years. Four patients (3.73 percent) were in radiologic stage 0, 38 patients (35.51 percent) were in radiologic stage I, 40 patients (37.38 percent) were in stage II, and 25 (23.36 percent) were in stage III. Thirty-eight patients (35.51 percent) had one or more extrapulmonary localization(s) of the disease. Positive association between sarcoidosis and HLA-B8 (chi 2 = 6.07, p = 0.0127, RR = 1.91) was confirmed. Regarding the age of onset of the disease, HLA-B35 was more frequent (chi 2 = 7.34, p = 0.0056, pc < 0.05, RR = 4.62) in patients with early onset of symptoms and/or signs, before the mean age of 36 years. With reference to the radiologic stage of the disease, HLA class II marker DR3 was more frequent in patients with stage I (chi 2 = 7.22, p = 0.0061, pc < 0.05, RR = 7.08). No significant relationship was found between sarcoidosis and HLA class III markers. These results seem to confirm an association of sarcoidosis with HLA classic genes and can sustain the hypothesis of a genetic heterogeneity of this disease.

Sarcoidosis and major histocompatibility complex genes with special emphasis on BF F subtypes.

Frequencies for HLA class I and II histoglobulins and C4A, C4B, BF complement proteins were performed for 59 sarcoidosis patients. The DR5 allele was present in 55.9% of patients as compared to 31.5% of controls. We noticed that its increase was more relevant in males and in those with a poor prognosis. BF F allele was significantly over-represented in patients (29.09% vs. 19.15% of control), especially in women. Special emphasis was given to BF F subtyping, to define an association between a particular BF F subtype and patient's sex or disease outcome.

Some properties of the alkaline proteinase from Aspergillus melleus.

Seaprose is a semi-alkaline proteinase produced by Aspergillus melleus. The aim of our study was to further characterize the properties of this enzyme, particularly looking at its interaction with alpha 1-proteinase inhibitor, the major human plasma proteinase inhibitor. We studied the cleavage of three synthetic peptide substrates induced by seaprose and the inhibitory profile of the enzyme by means of a panel of inhibitors, including alpha 1-proteinase inhibitor. The interaction between seaprose and alpha 1-proteinase inhibitor was also studied with SDS-PAGE. Finally, the elastolytic activity of seaprose was checked by means of bovine elastin solubilization. We found that seaprose cleaves preferentially the substrate containing a Phe residue in the P1 position. The inhibitory profile showed that seaprose is a serine-proteinase that cannot be inhibited by alpha 1-proteinase inhibitor. The SDS-PAGE revealed that alpha 1-proteinase inhibitor, after incubation with seaprose, underwent a limited proteolysis. Finally, seaprose 10(-2) M and 10(-3) M was able to solubilize bovine elastin. We conclude that seaprose is a serine-proteinase able to inactivate human alpha 1-proteinase inhibitor with limited proteolysis at (or near) the active site and that it has mild elastinolytic capacity.

Elevated serum procollagen III aminopeptide levels in sarcoidosis.

Procollagen III aminopeptide (P-III-P), a peptide released during the conversion of type III procollagen to type III collagen, is considered a potential marker of fibroblast activity in a variety of pulmonary and extrapulmonary diseases. The aim of the present article was to investigate the levels of P-III-P in serum samples (sP-III-P) from a large number of sarcoid patients, in particular looking at its relationship with other markers of disease activity and its presumed role as a marker of pulmonary fibrosis. sP-III-P has been radioimmunoassayed in an overall series of 57 patients and the levels were higher (19.18 +/- 9.17 ng/ml) than in 25 age- and sex-matched controls (11.32 +/- 2.15 ng/ml; p less than 0.001). The elevation was neither sex-related nor related to obvious liver sarcoid localization. Although sP-III-P levels were slightly higher in patients with stage II, there was no significant difference in patients with stage I or III. We found a positive relationship with serum angiotensin-converting enzyme (S-ACE) levels (p less than 0.04), but not with other markers of disease activity (67Ga uptake, bronchoalveolar lavage [BAL] lymphocyte percent, vital capacity, and lung diffusing capacity). The relationship with S-ACE was confirmed in a longitudinal follow-up study, where sP-III-P strictly paralleled the S-ACE behavior. Finally, the initial sP-III-P levels did not predict cases either with disease relapse or resistance to corticosteroid treatment. We conclude that, in our study, sP-III-P levels failed to characterize sarcoid patients with radiologic fibrotic pattern (stage III), and, in addition, were unable to predict which patients would have a poor prognosis. Rather, they reflect a metabolic activity of sarcoid granuloma cells. Thus, the usefulness of sP-III-P in the treatment of patients with sarcoid may be considered similar to that of S-ACE.