Rare SP-A alleles and the SP-A1-6A(4) allele associate with risk for lung carcinoma.

Next to cigarette smoking, genetic factors may contribute to lung cancer risk. Pulmonary surfactant components may mediate response to inhaled carcinogenic substances and/or play a role in lung function and inflammation. We studied associations between surfactant protein (SP) genetic variants and risk in lung cancer subgroups. Samples (n=308) were genotyped for SP-A1, -A2, -B, and -D marker alleles. These included 99 patients with small cell lung carcinoma (SCLC, n=31), or non-SCLC (NSCLC, n=68) consisting of squamous cell carcinoma (SCC, n=35), and adenocarcinoma (AC) (n=23); controls (n=99) matched by age, sex, and smoking status (clinical control) to SCLC and NSCLC; and 110 healthy individuals (population control). We found (a) no significant marker associations with SCLC, (b) rare SP-A2 (1A9) and SP-A1 (6A11) alleles associate with NSCLC risk when compared with population control, (c) the same alleles (1A9, 6A11) associate with risk for AC when compared with population (6A11) or clinical control (1A9), and (d) the SP-A1-6A4 allele (found in approximately 10% of the population) associates with SCC, when compared with population or clinical control. A correlation between SP-A variants and lung cancer susceptibility appears to exist, indicating that SP-A alleles may be useful markers of lung cancer risk.

TNF-alpha-, TNF-beta-, IL-6-, and IL-10-promoter polymorphisms in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major health problem. The disease is driven by abnormal inflammatory reactions in response to inhaled particles and fumes. Therefore, inflammatory mediators are postulated to be of distinct importance. In the present case-control study, we investigated interleukin (IL)-promoter polymorphisms known to correlate with altered transcription levels of their gene products in patients with COPD. We analyzed tumor necrosis factor-alpha (TNF-alpha)-308, TNF-beta-intron1-252, IL-6-174, IL-10-819, and IL-10-1082 polymorphisms in 469 individuals using restriction fragment length polymorphism-based converted polymerase chain reaction. The study population consisted of 113 patients with COPD based on chronic bronchitis, divided into subgroups by severity (I degrees -III degrees ), 113 matched hospitalized individuals suffering from severe coronary heart disease without pulmonary disease (age-, sex-, and smoking-matched control group), and 243 healthy individuals (population control group). The matched analysis showed no significant differences in genotype distribution of all tested polymorphisms between the matched controls and the COPD patients. However, comparison with the population controls revealed significant differences in IL-10-1082 A/G genotype frequencies (P = 0.0247 for the whole COPD group, P = 0.009 for smokers only), with the genotypes carrying the G allele more common in the COPD cases [odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.01-2.75; P = 0.046]. Interestingly, this shift toward more G alleles was even more pronounced in the matched control group (OR = 2.55, 95% CI 1.47-4.41; P = 0.0007), suggesting both presented groups share corresponding underlying mechanisms. The IL-10-1082_G allele is known to correlate with altered IL-10 levels. Therefore, it might be associated with altered or abnormal inflammatory response, a mechanism that could be postulated to be important in both chronic bronchitis and coronary heart disease.

[64-year old woman patient with severe pain and alterations of sensibility]. / 64-jährige Patientin mit starken Schmerzzuständen und Sensibilitätsstörungen.

The differential diagnosis of chronic pain is not seldom difficult, particularly if additional symptoms or laboratory tests are not specific, and small but important signs are not correctly analyzed and overlooked. We present a case of sarcoidosis with central involvement showing these diagnostic problems.

[Effect of subcutaneous fatty tissue on normal respiratory sounds]. / Der Einfluss der subkutanen Fettschicht auf die normalen Atemgeräusche.

Auscultation is an important, non-invasive and simple measure in the diagnosis of lung diseases that can detect sometimes pathological processes prior to radiography. Attempts have already been made to automatically detect characteristic pathological sounds, but a knowledge of potential influencing factors is a must for correct interpretation. In this study we have investigated the effect of the subcutaneous fat layer on normal lung sounds. This is of importance to determine corrective factors for the automatic detection of bronchial breathing in pneumonia. The lung sounds of 125 healthy people (55f, 70m) were digitally recorded at four different positions of the thorax (3. ICR paravertebral, 7. ICR medioscapular, all left and right). Evaluation was done separately for gender. The subcutaneous fat layer was measured with a Holtain Skinfold Caliper at the identical four recording positions. For a quantitative evaluation of the sounds we calculated the relative power of frequency bands 330-600 Hz and 60-330 Hz and their ratio. The relation between these parameters and the subcutaneous fat layer was analyzed with the Pearson correlation. The results of this study show that the influence of subcutaneous fat layer is negligible and can be ignored in the automatic detection of lung sounds.

Detection of bronchial breathing caused by pneumonia.

The classic auscultation with stethoscope is the established clinical method for the detection of lung diseases. The interpretation of the sounds depends on the experience of the investigating physician. Therefore, a new computer-based method has been developed to classify breath sounds from digital lung sound recordings. Lung sounds of 11 patients with one-sided pneumonia and bronchial breathing were recorded on both the pneumonia side and on contralateral healthy side simultaneously using two microphones. The spectral power for the 300-600 Hz frequency band was computed for four respiratory cycles and normalized. For each breath, the ratio R between the time-segments (duration = 0.1 s) with the highest inspiratory and highest expiratory flow was calculated and averaged. We found significant differences in R between the pneumonia side (R = 1.4 +/- 1.3) and the healthy side (R = 0.5 +/- 0.5; p = 0.003 Wilcoxon-test) of lung. In 218 healthy volunteers we found R = 0.3 +/- 0.2 as a reference-value. The differences of ratio R (delta R) between the pneumonia side and the healthy side (delta R = 1.0 +/- 0.9) were significantly higher compared to follow-up studies after recovery (delta R = 0.0 +/- 0.1, p = 0.005 Wilcoxon-test). The computer based detection of bronchial breathing can be considered useful as part of a quantitative monitoring of patients at risk to develop pneumonia.

Surfactant protein B gene variations enhance susceptibility to squamous cell carcinoma of the lung in German patients.

Genetic factors are thought to influence the risk for lung cancer. Since pulmonary surfactant mediates the response to inhaled carcinogenic substances, candidate genes may be among those coding for pulmonary surfactant proteins. In the present matched case-control study a polymorphism within intron 4 of the gene coding for surfactant specific protein B was analysed in 357 individuals. They were divided into 117 patients with lung cancer (40 patients with small cell lung cancer, 77 patients with non small cell lung cancer), matched controls and 123 healthy individuals. Surfactant protein B gene variants were analysed using specific PCR and cloned surfactant protein B sequences as controls. The frequency of the intron 4 variation was similar in both control groups (13.0% and 9.4%), whereas it was increased in the small cell lung cancer group (17.5%) and the non small cell lung cancer group (16.9%). The gene variation was found significantly more frequently in patients with squamous cell carcinoma (25.0%, P=0.016, odds ratio=3.2, 95%CI=1.24-8.28) than in the controls. These results indicate an association of the surfactant protein B intron 4 variants and/or its flanking loci with mechanisms that may enhance lung cancer susceptibility, especially to squamous cell carcinoma of the lung.

Effect of N-acetylcysteine treatment on NO2-impaired type II pneumocyte surfactant metabolism.

Inhalation of nitrogen dioxide (NO2) is known to alter the composition of the bronchoalveolar lavage (BAL) and to impair the surfactant metabolism of type II pneumocytes. However, information is sparse as to whether application of the widely used antioxidant N-acetylcysteine (NAC) is capable of preventing or reducing these alterations. The aim of the study was to investigate if in vivo administration of NAC to NO2-inhaling rats protected BAL parameters and physiology of type II pneumocytes from impairment. For this purpose, rats were exposed to 720 p.p.m. h-1 NO2, that was applied continuously, intermittently or repeatedly. During inhalation one group of rats received saline and the other group received NAC antioxidant (200 mg kg-1, intraperitoneally) once a day. The BAL protein and phospholipid content increased most in the continuously and repeatedly NO2-exposed rats when compared to the controls, while the intermittent exposure did not change these parameters. Application of NAC led to a marked decrease of the protein elevation for the continuously and intermittently exposed groups, but exhibited no influence on the BAL phospholipid. Surprisingly, all NO2 exposure modes elevated the glutathione content (reduced and oxidized) in the BAL. Application of NAC clearly decreased the content of both forms of glutathione in the continuously and the repeatedly NO2-exposed groups. Phospholipid synthesis, measured by choline uptake into type II cells, was increased most after continuous NO2 inhalation. The NAC reduced this increase moderately. Whereas choline uptake by type II cells was obviously stimulated by NO2, the stimulated secretion of phosphatidylcholine from these cells was decreased by this oxidant. Only continuous exposure reduced this activity markedly. The NAC clearly restored the impaired secretion activity in the cells from the continuously NO2-exposed animals. Since the efficacy of NAC in the prevention of NO2-induced impairments in the surfactant system is striking mainly in the continuously exposed group, we suggest that administration of NAC to NO2-induced lung injury partially restores altered BAL components and the impaired physiology of type II pneumocytes.

Effects of the nitric oxide/cGMP system compared with the cAMP system on airway mucus secretion in the rat.

Mucus secretion of the airways is under the control of a variety of intracellular second messenger systems. Cyclic nucleotides such as cGMP, coupled to the recently discovered nitric oxide system, and cAMP are of outstanding interest in this respect. The present study used the modified Ussing chamber technique and mucins labelled with (35)SO(4) to investigate mucus secretion in the rat trachea to clarify the contribution of these different second messenger systems to the control of mucin secretion.A variety of drugs affecting either the generation or the breakdown of the respective cyclic nucleotides were used. Neither drugs interfering with nitric oxide synthase nor the phosphodiesterase isoenzyme responsible for cGMP breakdown nor cGMP analogues were able to affect mucus secretion. In contrast, stimulation of adenylate cyclase or inhibition of the respective phosphodiesterase resulted in a potent increase of mucus secretion. In conclusion, we failed to show the involvement of the nitric oxide/cGMP system, whereas the cAMP system seems to be a very efficient regulator of mucus secretion in the rat trachea.

[Eosinophilic myocarditis in Churg-Strauss syndrome. A rare cause of left heart decompensation with lung edema]. / Eosinophile Myokarditis bei Churg-Strauss-Syndrom. Seltene Ursache einer Linksherzdekompensation mit Lungenödem.

HISTORY: A 50-year-old woman was admitted because of marked dyspnoea at rest and signs of left heart failure with pulmonary oedema. 9 years ago, the diagnostic constellation of bronchial asthma, polyneuropathy, pericardial effusion and eosinophilia had indicated Churg-Strauss syndrome. Since then she had remained symptom-free under maintenance doses of azathioprine (for 2 years) and gradually reduced doses of steroids. INVESTIGATIONS: Chest X-ray showed signs of pulmonary congestion and cardiomegaly, echocardiography demonstrating enlargement of the left heart with marked impairment of ventricular function, and both revealed pericardial effusion. The electrocardiogram showed complete absence of R waves and ST elevation in leads V1-V5. Coronary angiography excluded coronary artery disease. Myocardial biopsy contained signs of active but no longer acute myocarditis with eosinophilic tissue infiltration and microgranulomas. White blood cell count was normal, but there was marked eosinophilia (39%). IgE was elevated (601 kIU/l). DIAGNOSIS, TREATMENT AND COURSE: In view of the good therapeutic effects 9 years ago, this relapse of Churg-Strauss syndrome with eosinophilic myocarditis was again treated with azathioprine and steroids. In addition, diuretics, digitalis and ACE-inhibitors successfully treated the heart failure. In the course of treatment the signs of inflammation, including the eosinophilia, regressed or became normal. CONCLUSION: After a 10-year remission without complication of a Churg-Strauss syndrome the onset of cardiac signs is the decisive long-term prognostic factor.

The relationship between normal lung sounds, age, and gender.

Auscultation is one of the most important noninvasive and feasible methods for the detection of lung diseases. Systematic changes in breathing sounds with increasing age are of diagnostic importance. To investigate these changes, we recorded lung sounds taken from four locations in the posterior thorax of 162 subjects, together with airflow. The data were analyzed according to age, sex, and smoking habit. In order to describe the power spectrum of the lung sounds, we calculated mean and median frequency, frequency with the highest power, and a ratio (Q) of relative power of the two frequency bands of 330 to 600 Hz and 60 to 330 Hz. Linear regression analysis was used as a measurement of age-dependence of these variables. Significant differences in Q were found in men versus women (p < 0.05), but not in smokers versus nonsmokers. Within the groups, a small but significant correlation existed between Q and age (r(2) /= +/- 5%) have no clinical significance and need not to be considered in the automatic detection of lung diseases by analyzing lung sounds.