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Background: Pulmonary hypertension (PH) is prognosti- cally important in chronic obstructive pulmonary disease (COPD). Since PH only weakly correlates with hypoxemia, other factors must play a role. Objective: To investigate whether polymorphisms of the serotonin transporter (5HTT), serotonin-2a receptor (5HTR2a) and endothelial nitric oxide synthetase (eNOS) are related to PH in COPD. Methods: In 59 COPD patients who underwent right heart catheterization, 6-min walking distance, NYHA functional class, pulmonary function tests, blood gases and 5HTT, 5HTR2a and eNOS (4ab and T298C) polymorphisms were determined. Results: Forty-nine COPD patients in NYHA functional class III–IV were included. Ten were excluded due to comorbid causes of PH (mainly chronic thromboembolic). PH (mPAP ≧25 mm Hg) was present in 55% and usually mild, but out of proportion (mPAP ≧40 mm Hg) in 12%. Patients with PH had significantly higher frequencies of the 5HTT-L-allele (52%) compared to individuals without PH (36%), and LL homozygote patients had more severe PH. In patients with out-of-proportion PH, the L-allelic frequency was even 75%. We found no association of 5HTR2a and eNOS polymorphism with PH in COPD. Conclusions: In this COPD cohort we confirm that PH is frequent and usually mild, but out of proportion in a subgroup. We found a significant association of the L-allelic variant of 5HTT with PH overall and especially in out-of-proportion PH. These findings may point towards a role of the serotonin system in COPD-PH and warrant further studies.

We report a 57-year-old female with severe airway obstruction who underwent resection of a tumor of unknown dignity during lung volume reduction surgery. The nodule consisted of a well-differentiated neuroendocrine tumor (carcinoid), and severe chronic obstructive lung disease was due to diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, a very rare cause of obliterative bronchiolitis. Radionuclide ablative therapy of the neuroendocrine tissue was considered but not found to be feasible due to a low lung/background ratio of the radiotracer.

Background: Alveolitis and the production of proinflammatory cytokines are known features of sarcoidosis. Because of the usually spontaneous resolution of alveolitis despite local secretion of mediators causing inflammation and granuloma formation, we hypothesized that downmodulating mechanisms such as anti-inflammatory cytokines might be involved in this process. Objective: Investigation of the secretion of the macrophage deactivating cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) by alveolar macrophages in untreated sarcoidosis of the lung. Methods: Fourteen consecutive and untreated patients with pulmonary sarcoidosis and 18 volunteers underwent bronchoscopy. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and the secretion of IL-10 and TGF-β was studied. Results: Spontaneous IL-10 production by AM was found in 6 of 14 patients and in 2 of 18 controls. The IL-10 level of lipopolysaccharide-stimulated AM was significantly higher in patients. Monocytes secreted significantly more IL-10 than AM, but there was no difference between sarcoid and control monocytes. No difference was found in the secretion of TGF-β between patients and controls. Conclusion: Increased local secretion of IL-10 – but not TGF-β – may represent a downmodulating mechanism involved in the spontaneous resolution of alveolitis in sarcoidosis.

Background: The Epworth Sleepiness Scale (ESS) is a questionnaire widely used in English speaking countries for assessment of subjective daytime sleepiness. Objective: Our purpose was to translate and validate the ESS for use in German-speaking countries. Methods: A German translation of the ESS was administered to 159 healthy German-speaking Swiss and to 174 patients with various sleep disorders. Results: The mean ± SD of ESS scores in normals was 5.7 ± 3.0, in patients it was 13.0 ± 5.1 (p < 0.001). Scores were not correlated with age or gender but with the percentage of time spent at an oxygen saturation Conclusions: Our data validate the ESS for application in German-speaking populations. The simplicity, reliability and the apparent lack of relevant influences of language and cultural background on performance of the ESS makes it a valuable tool for clinical management and research.

Lung transplant bronchiolitis obliterans syndrome (BOS) is the most significant long-term cause of morbidity and mortality after lung transplantation. Although augmented immunosuppression is used by most centers, reported on treatment to reverse BOS are largely anecdotal. We performed a double-blind, randomized, controlled trial (RCT) with ten treatment pairs of 2 weeks duration each comparing inhaled fluticasone propionate (2 x 1,000 micrograms/day) with placebo in a patient with BOS grade 2 who previously showed an improvement in lung function after inhaled steroids. The Baseline Dyspnea Index and the Modified Medical Research Council Dyspnea Scale showed a significant improvement during fluticasone treatment compared with the placebo period (2.7 +/- 0.2 vs. 2.0 +/- 0.3; p = 0.043; and 1.7 +/- 0.2 vs. 2.4 +/- 0.2; p = 0.043). The patient correctly identified fluticasone and placebo, respectively, in eight of ten trial pairs (p = 0.016). The values of forced expiratory volume in 1 s were significantly higher during the fluticasone period (1,207 +/- 10 ml; 95% confidence interval, CI, 1,187-1,227 ml) compared to the placebo period (1,150 +/- 6 ml; 95% CI 1,138-1,162 ml; p = 0.0012). In conclusion, this n-of-1 RCT suggests the efficacy of high-dose inhaled fluticasone in our patient with lung transplant BOS. We propose to conduct a multicenter RCT of high-dose inhaled steroids. Until further data are available, this treatment modality should be offered to patients with lung transplant BOS.

The purposes of our study were (1) to investigate whether a 3-min short-term hyperventilation leads to posthyperventilatory hypoxemia and (2) to assess the role of transcutaneous blood gas measurements for monitoring oxygen and carbon dioxide changes during the after the test. In 10 male volunteers arterial and transcutaneous blood gases were measured simultaneously before, during and after a 3-min voluntary hyperventilation maneuver. Baseline arterial PO2 increased from 13.7 +/- 0.4 kPa (103 +/- 3 mm Hg) to 18.6 +/- 0.3 kPa (139 +/- 2.3 mm Hg; p0.005 compared to baseline) during hyperventilation. After the provocation test posthyperventilatory hypoxemia occurred with a minimal mean value of 7.8 +/- 1.3 kPa (58.5 +/- 9.8 mm Hg; p0.05 compared to baseline). Whereas close agreement between arterial and transcutaneous measurements was obtained for carbon dioxide values before hyperventilation, transcutaneous O2 consistently underestimated arterial O2. A short-term over-breathing of 3 min causes a significant posthyperventilatory hypoxemia. We hypothesize that posthyperventilatory hypoxemia is caused by hypopnea as a result of depleted CO2 body stores. Noninvasive transcutaneous blood gas measurements are not reliable for monitoring blood gas changes during and after hyperventilation, most probably because of the slow response time of the electrodes and the reflex vasoconstriction of the skin vessels.

To investigate the local immunological situation in the lung of HIV-infected patients with Pneumocystis carinii pneumonias (HIV-PCP), we analyzed the proportion and the distribution of lymphocyte subpopulations and their state of activation in bronchoalveolar lavage (BAL) and peripheral blood of 21 HIV-PCP patients (CDC classification group IV) compared to 24 HIV-negative patients with interstitial lung diseases (ILD). Peripheral blood lymphocytes (PBL) and BAL cells were stained with monoclonal antibodies. Two-color cytofluorometric analysis (flow cytometry) was performed with a cytofluorograph (Epics Profile, Coulter Corp., Hialeah, Fla., USA). In BAL from HIV-PCP patients the number of CD3-positive lymphocytes was significantly increased, yet there was no difference in the number of macrophages and neutrophils when compared to patients with ILD. Quantification of lymphocyte subpopulations showed that the increased number of BAL CD3-positive lymphocytes in HIV-PCP patients was mainly due to a significantly increased number of CD8-positive T cells, while the pulmonary CD4-positive T cells were decreased both in relative and absolute numbers. As a consequence, an inverted pulmonary CD4/CD8 ratio resulted for HIV-infected patients with PCP. Analysis of in-vivo-activated T cells in BAL and peripheral blood when measured by the expression of IL-2R, HLA-DR and VLA-1 revealed increased numbers of IL-2R and HLA-DR bearing CD8-positive T cells but significantly decreased numbers of IL-2R and HLA-DR bearing CD4-positive T cells as well as a higher number of CD8/CD57 double positive T cells in HIV-infected individuals when compared to patients with ILD.(ABSTRACT TRUNCATED AT 250 WORDS)

Sixty episodes of Pneumocystis carinii pneumonia in 59 patients were evaluated for risk factors predicting fatal outcome within 14 days after bronchoscopy. We found significantly higher values for serum lactate dehydrogenase (p less than 0.001), alveolar-arterial oxygen difference (p less than 0.001) and percentage of bronchoalveolar lavage neutrophils (p less than 0.001) in patients dying within 14 days, but there was considerable overlap of these variables between the two groups. Using a score system combining the three parameters allowed however an excellent discrimination between the two groups.

A patient suffering from multiple episodes of fever and chills due to septic pulmonary emboli is reported. Hereditary hemorrhagic telangiectasia was involving the mucous membranes of his oral cavity and the stomach but not the pulmonary vascular bed. Since no other infectious embolic sources were found and the patient's pulmonary infection was not extirpated by a prolonged course of antibiotics but only cured after surgical treatment of multiple periodontal abscesses, we speculate that gingival arteriovenous malformations being involved by periodontitis were the source of small septic emboli.

Accessible online at: www.karger.com/journals/res In Europe, lung cancer is the most frequent lethal neoplasm among men, and its incidence is rapidly rising in women. Sadly enough, early diagnosis and treatment still have a low impact on the survival of patients with this type of cancer. Risk estimates for lung cancer vary largely from one country to another. This can be attributed to several sources of variation: factors inherent in data collection, smoking habits in the different study populations and distribution of confounders and effect modifiers. It is well known that cigarette smoking is the major risk factor for lung cancer. In 10 case-control studies carried out in 6 European countries, which included 7,609 cases of lung cancer and 10,431 controls, odds ratios of 29.9 were found in men and 8.7 in women with attributable risks exceeding 90% for men and 60% for women [1]. With an annual age-standardized incidence rate of 61.6 per 100,000, Turkey has the highest lung cancer incidence rate for men worldwide [2]. The incidence is much lower in females (5.1 per 100,000), and is also considerably lower than in the USA and the UK [3]. This reflects the smoking habits of the Turkish population, where, as reported by Gaskell [4] in this issue of Respiration, the percentage of female smokers is less than half that of male smokers. A particular aspect of this study is the high proportion of patients with squamous cell carcinoma (40%). This situation is comparable to that in other countries a few decades ago. In the meantime, the proportion of adenocarcinomas among lung cancers has been increasing. Improved pathologic typing has resulted in a decrease in the number of cancers classified as undifferentiated and the appropriate use of WHO definitions has resulted in many tumors formerly classified as large cell tumous being reclassified as adenocarcinoma. However, the reported increase in the proportion of adenocarcinomas cannot be explained by these factors alone. The increase in the proportion of adenocarcinomas is paralleled by a decrease in the proportion of squamous cell carcinomas and, to a lesser extent small cell cancers [5–7]. The reason for this shift is not entirely clear. It is most likely attributable to the changes in smoking habits. Smoke of unfiltered cigarettes contains large particles, which are deposited in the more central airways, whereas smoke of low-yield filter-tipped cigarettes, which is inhaled more deeply and contains smaller potentially carcinogenic particles, is associated with more peripherally located cancers, i.e. adenocarcinomas. It can be assumed, that within the following years smoking habits will change also in Turkey, which will result in a shift with an increasing proportion of adenocarcinomas and a decrease in squamous cell carcinomas. If it is not possible to stop the smoking pandemia, it is foreseeable that the rate of lung cancer will continue to grow particularly among women. This is sad since the 5year survival has not substantially increased over the last two decades and early detection is of yet unproven impact on overall lung cancer mortality.