[Smoking causes chronic obstructive lung diseases and increased infections of the respiratory tract]. / Rauchen verursacht chronisch obstruktive Lungenerkrankungen und gehäufte Infekte des Respirationstraktes.

The lung is the first target organ which is affected in its structure and function by inhalation of cigarette smoke The lung and the airways are working virtually as a filter for several hundred damaging substances, which are contained in cigarette smoke. As a consequence cigarette smokers are showing a markedly elevated prevalence for development of airway obstruction, and clinical symptoms leading to chronic obstructive pulmonary diseases (COPD) as well as to recurrent respiratory tract infections. As a result smokers are showing an elevated mortality rate caused by lung cancer as well as by development of COPD. The irritating and damaging activity of cigarette smoke to the lung is dose dependent. It is concluded that cigarette smoking is by far the largest preventable risk factor for development of chronic lung diseases.

[Do light cigarettes decrease the risk of smoking?]. / Verringern Leichtzigaretten das Risiko des Zigarettenrauchens?

Since the introduction of filter cigarettes in the sixties and early seventies, a reduction of the risk for lung cancer could be observed (20 to 40%). However, a further reduction of tobacco smoke ingredients by smoking modern light cigarettes (tar content below 10 mg) is questionable because of compensation of smoking behaviour by the individual smoker. A further reduction of risk to contract lung cancer by smoking light cigarettes therefore is not probable and supportive data are not available. Smoking of light cigarettes is not likely to result in a significant decrease of the risk for myocardial infarction or cardiac death as well as for chronic lung diseases. Promotion of light cigarettes by the tobacco industry is suggesting that each smoker could significantly diminish his risks just by selecting the right type of cigarettes. This is not supported by long term clinical studies. Such promotion, however, provides the smoker with further arguments to continue smoking. Ultra light cigarettes (tar content below 3 mg) could potentially diminish the risk but are hardly accepted by current smokers. Despite strong promotion and advertisement ultra light cigarettes had not been successful on the market.

[Vitronectin in bronchoalveolar lavage--a parameter of disease activity in sarcoidosis]. / Vitronectin in der bronchoalveolären Lavage--ein Aktivitätsparameter bei Sarkoidose.

Vitronectin is a multifunctional glycoprotein which is involved in several of the processes of inflammation and repair. In previous studies we demonstrated that increased concentrations of vitronectin can be detected in bronchoalveolar lavage fluids (BAL) of patients with interstitial lung disease (e.g. sarcoidosis). The outcome of sarcoidosis is generally favorable, however, some patients progress to pulmonary fibrosis. There is a need for markers indicating early fibrotic changes in the lung in patients with sarcoidosis. The present study was designed to evaluate the potential of BAL-vitronectin measurements for the assessment of disease activity in subjects with sarcoidosis. BAL-vitronectin concentrations were determined in 19 patients with biopsy proven sarcoidosis and sequential analysis of BAL-vitronectin levels were performed in 11 patients before and after therapy. Patients with active sarcoidosis had higher BAL-vitronectin concentrations (1.56 +/- 0.89 microgram/ml) than patients with inactive disease (0.68 +/- 0.33 microgram/ml; p < 0.01). Patients with active sarcoidosis received high-dose glucocorticoid treatment for four weeks followed by low-dose glucocorticoid therapy for eleven months. After high-dose medication BAL-vitronectin concentrations fell significantly (1.08 +/- 0.9 microgram/ml; p < 0.01). A further decrease in vitronectin levels resulted when therapy was continued for a year (0.75 +/- 0.48 micrograms/ml). Clinical deterioration correlated with an increase in BAL-vitronectin concentrations. Thus, measurement of BAL-vitronectin levels might be a useful marker for assessing disease activity and response to therapy in patients with sarcoidosis, but does not provide prognostic information.

Serum procollagen III peptide levels in subjects with sarcoidosis. A 5-year follow-up study.

In a prospective study, Type III procollagen N-terminal peptide was measured in the sera of 38 subjects with biopsy-proven pulmonary sarcoidosis at 6-month intervals over a period of 5 yr. The subjects were divided into four groups according to their radiologic presentation and clinical course: Group A (n = 10) subjects with sarcoidosis Type I without radiologic progression over 5 yr; Group B (n = 5) subjects with sarcoidosis Type I with radiologic progression to Stage II or III; Group C (n = 9) subjects with sarcoidosis Types II and III without progression over 5 yr; and Group D (n = 14) subjects with sarcoidosis Types II and III with radiologic progression. Lung function tests (FVC, FEV1, and DLCO), chest roentgenograms, and measurements of serum angiotensin converting enzyme (S-ACE) were performed concurrently with the S-PCP-III levels. Significantly higher levels of S-PCP-III were found in group B (Type I, progressive) (18.2 +/- 1.09 ng/ml) and in group D (Type II/III, progressive) (13.9 +/- 1.2 ng/ml) compared with those of Group A (Type I, stable) (9.1 +/- 1.09 ng/ml) and Group C (Type II/III, stable) (7.6 +/- 1.1 ng/ml) or normal volunteers (9.4 +/- 4 ng/ml) (p less than 0.001 for all comparisons). Changes in S-PCP-III levels tended to parallel the clinical course, and steroid treatment resulted in a significant decrease in S-PCP-III concentrations (p less than 0.001). In contrast, serum angiotensin converting enzyme (S-ACE) levels did not correlate with either the clinical course or radiologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Urine excretion of inhaled technetium-99m-DTPA: an alternative method to assess lung epithelial transport.

Technetium-99m DTPA clearance (99mTc-DTPA) clearance measured by a gamma camera or a scintillation probe not only reflects epithelial transport, but is also influenced by an unknown amount of mucociliary clearance depending on particle size and aerosol deposition. This is confirmed by factor analysis of dynamic inhalation studies. Assessment of epithelial absorption by urinary excretion of inhaled 99mTc-DTPA is largely independent of aerosol lung deposition. Twenty-four-hour excretion reflects the amount of aerosol cleared by absorption, while two-hour excretion is a quantitative measure of the aerosol absorption rate from the epithelium into blood. Urinary 99mTc-DTPA excretion of two aerosols with different particle size correlated significantly (p less than 0.001) with analysis of lung clearance curves. A very similar regression in the form of a cumulative exponential function was found with both aerosols. Two-hour urine values of nonsmokers differed significantly from those of smokers or patients with active interstitial or infectious lung disease. This alternative procedure is suited as a bedside test and holds promise for patient monitoring and follow-up.

[Sarcoidosis as a multi-organ disease]. / Die Sarkoidose als Multiorganerkrankung.

Sarcoidosis meets the criteria for multi-organ disease, which differs from systemic disease in the following points: The preferred primary organ (lungs) is known, immunological processes take place only in the organs involved (T helper lymphocyte accumulation), the clinical picture depends upon the organ involvement, and granulomas are typical of the disorder. The clinical significance of the various organ manifestations covers a broad spectrum, which can also include a threat to life (myocardium), blindness, chronic invalidism (pulmonary fibrosis, hepatopathy, nephropathy), and cosmetic impairment (cutaneous sarcoidosis). Numerous organ manifestations have no clinical significance, and some are both rare and limited (tumorous CNS involvement). So-called overlap syndromes have characteristic features common to both multi-organ and systemic diseases. In addition to characteristic sarcoidosis manifestation in an organ, signs of a generalized disorder are also detectable. Examples are primary biliary cirrhosis, Crohn's disease, coeliac disease, Whipple's disease, TASS (Thyrotoxicosis, Addison, Sjögren, Sarcoidosis) as lymphomas and inflammatory diseases (tuberculosis). Outside of the primary organ, these manifestations are often clinically latent. Selective investigations bronchoalveolar lavage), however, can demonstrate the presence of sarcoidosis alveolitis. It is demonstrated that for the clinician, differentiation of multi-organ from systemic disease is meaningful in particular with respect to therapeutic consequences. In the individual case, however, possible overlapping must always be borne in mind.

[Assessment of different clearance mechanisms of the lung using factor analysis]. / Beurteilung unterschiedlicher Clearancemechanismen der Lunge mit Hilfe der Faktoranalyse.

Measurement of epithelial clearance over the lungs is always influenced by mucociliary transport since the lung is a 3-dimensional organ where ciliated and respiratory epithelia overlap. Factor analysis provides factor images and time-activity curves of extracted physiological factors corresponding to specific structures, even if these structures overlap. In 16 inhalation studies of 99m Tc-DTPA aerosol, factor analysis always extracted 2 factors with opposite temporal behavior, one corresponding to epithelial and one to mucociliary transport. Clearance rates measured over the lungs were significantly lower than epithelial transport-related factor curve values (1.35%/min vs 2.2%/min), but were identical with the clearance rates of the sum of both factors plus factor background. Factor analysis allows quantitative assessment of epithelial transport without interference of other clearance mechanisms and should be evaluated further in different pulmonary disorders.

Expression of the VEP13 antigen (CD16) on native human alveolar macrophages and cultured blood monocytes.

Human alveolar macrophages (AM phi) from thirteen patients, who were suffering from various lung diseases were harvested by bronchoalveolar lavage. Peripheral blood monocytes from eight healthy donors were isolated by Ficoll-Hypaque gradient centrifugation and adherence to plastic surface. To detect the VEP13 antigen (CD16) on these cells, a rosette assay employing ox erythrocytes coated by the CrCl3 method with purified VEP13 monoclonal antibody (Eo-VEP13) was used. A mean of 31.3% of freshly isolated AM phi and 3.9% of blood monocytes formed Eo-VEP13 rosettes. Monocytes cultured for 3 or 6 days in the presence of a supernatant from mouse L929 cells, which had been shown previously to improve long-term viability of human monocytes in culture, showed 12.5% and 25.3% Eo-VEP13 rosettes, respectively. No significant increase in VEP13 antigen expression was noted by culturing monocytes without L929 cell supernatant. The factor in L929 supernatant that induces VEP13 antigen expression has not been identified. Tunicamycin at 10 micrograms/ml inhibited significantly VEP13 antigen expression on monocytes. In contrast, IgG rosette formation was not reduced by tunicamycin. Our data show that subpopulations of native human AM phi and peripheral blood monocytes cultured in presence of a supernatant of L929 fibroblasts containing mainly murine CSF may express the CD16 antigen, which is normally found on large granular lymphocytes (LGL). Suppression by tunicamycin indicates that Fc receptor glycosylation takes place during a later differentiation step of mononuclear phagocytes.

Neutrophil elastase alpha 1-proteinase inhibitor complexes in pleural effusions.

Polymorphonuclear (PMN) granulocyte derived neutrophil elastase (NE) is rapidly antagonized by alpha 1-proteinase inhibitor (alpha 1 PI) in vivo. To determine the clinical value of elastase alpha 1-proteinase inhibitor complexes (E-alpha 1 PI) in pleural effusions, fluid samples of 99 patients were examined. Fifty-six had malignant effusions, 30 had non-malignant exudates (pleural protein above 3 g/dl) mainly of inflammatory origin, and 13 patients had low protein transudates (below 3 g/dl) due to congestive heart failure. Nonmalignant exudates showed significantly higher (P less than 0.001) concentrations of E-alpha 1 PI compared with malignant effusions or low protein transudates (P less than 0.001). Malignant exudates secondary to lung cancer were characterized by higher (P less than 0.001) median pleural E-alpha 1 PI concentrations compared to malignant exudates due to primarily extrathoracic malignancies. Total pleural leukocyte counts and pleural neutrophil counts were performed in 68 effusions. By this means no clear-cut differentiation between malignant and nonmalignant exudates seems possible except for marked empyema. In conclusion, E-alpha 1 PI complexes in pleural fluid may better reflect the stage of inflammation of pleural effusions rather than mere pleural leukocyte counts. Low levels of E-alpha 1 PI complexes (less than 75 ng/ml) in pleural exudates with protein values above 3 g/dl are characteristic of malignant exudates. Determination of E-alpha 1 PI in pleural exudates may serve as a sensitive marker of inflammation and useful adjunct to pleural cytology in aspects of differential diagnosis of pleural effusions.

[Diagnosis and therapy of nocturnal asthma]. / Bemerkungen zur Diagnostik und Therapie des nächtlichen Asthmas.

The bronchial tonus depends on circadian oscillations like all other organ functions. The tendency to increased nocturnal bronchoconstriction in some asthmatic subjects is well known. The reasons of such individual variations are different concentrations of cortisol, adrenaline, histamine, cAMP in serum as well as imbalance between vagal and sympathetic interactions. In practice, the early diagnosis of severe nocturnal bronchial constriction is important for prevention of asthma attacks and status asthmaticus. We report on our circadian measurements of airway resistance (Ros) or peak-flow. By adequate therapy an improvement of the individual bronchial tolerance could be achieved, however the biorhythm remained unchanged. Measurements of airway resistance at 2 a.m. were significantly improved by therapy, as was the mean level measurements during 4-hourly readings. High dose bedtime or slow release theophylline decreased the number of nocturnal asthma attacks.