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Abstract Background and methods Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR. Results We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 105 viral copies/ml in nasal lavage and 1.88 × 105 viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD. Conclusion HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.

Chronic obstructive pulmonary disease (COPD) and asthma are common complex diseases characterized by airflow obstruction and inflammatory processes in the small airways. lnterleukin 8 (IL-8) is a potent proinflammatory cytokine which interacts with the IL-8 receptora(IL8RA, CXCR1) andß(IL8RB, CXCR2), leading to activation and migration of leukocytes. In order to evaluate the role of the IL8RA gene in the pathogenesis of COPD and asthma, we screened the coding region of IL8RA for mutations by means of single-strand conformation polymorphism analysis in 50 COPD patients and identified three exchanges (M31R, S276T and R335C). These three polymorphisms were subsequently genotyped in 182 adult patients with COPD, 68 adult patients and 130 children with asthma as well as 454 healthy controls. The frequencies of the IL8RA 31R and 335C alleles were significantly increased in patients with COPD and in children with asthma compared to healthy controls (P=0.0073 and 0.023, respectively). Thus, these polymorphisms may play a role in the pathogenesis of COPD and asthma.Genes and Immunity (2005) 6, 225-230. doi:10.1038/sj.gene.6364181 Published online 17 March 2004 [ABSTRACT FROM AUTHOR]

Objectives: Hair bleaches containing persulphates have been identified as the cause of occupational asthma in hairdressers. Also employees in persulphate production with occupational asthma have been described. It was the aim of this study to give an estimate of the prevalence of asthma due to persulphates in chemical workers with exposure to ammonium and sodium persulphate.Methods: A cross sectional study was performed in 32 of 33 employees of a persulphate producing chemical plant. Eighteen of 23 workmen from the same plant with no exposure to persulphates were taken as controls. Also, information was collected from medical records of the seven subjects who had left the persulphate production for medical reasons since 1971. Data were recalled by a questionnaire, skin prick tests were performed with five environmental allergens, and ammonium and sodium persulphate (80 mg/ml). Specific immunoglobulin E (IgE) to the same environmental allergens as in the skin test, and total IgE were measured. Lung function and bronchial responsiveness to histamine were assessed by standard procedures. Workplace concentrations of ammonium and sodium persulphate were estimated by area and personal monitoring. The amount of persulphate was analysed as sulphur by inductively coupled plasma emission spectrometry.Results: Work related rhinitis was reported by one subject with exposure to persulphates, conjunctivitis and bronchitis were reportedly related to work by two controls. There were no cutaneous reactions to persulphates in either group. Four non-atopic subjects exposed to persulphates, and two controls, one atopic and one non-atopic, were considered to be hyperresponsive to histamine. Three subjects exposed to persulphates with bronchial hyperresponsiveness (provocation dose of histamine causing a 15% fall in forced expiratory volume in one second (PD15 FEV1) < or = 1 mg) did not show variability in peak expiratory flow of > or = 20%, the rest refused peak flow measurements. None of the variables showed significant differences between the groups (P > 0.05). Six of the exworkers left because of work related contact dermatitis. Mean values for workplace concentrations of ammonium and sodium persulphate within the bagging plant were below 1 mg/m3, and the maximal concentrations were 1.4 mg/m3 and 3.6 mg/m3, respectively.Conclusion: Exposure to workplace concentrations of ammonium and sodium persulphate of about 1 mg/m3 in this chemical plant was not associated with a risk of occupational asthma. [ABSTRACT FROM AUTHOR]

Abstract Background Data on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN)-γ release assays (IGRAs) in the serial testing of health care workers (HCWs) is limited. The objective of the present study was to determine the frequency of IGRA conversions and reversions and to identify predictors of persistent IGRA positivity among serially tested German HCWs in the absence of recent extensive tuberculosis (TB) exposure. Methods In this observational cohort-study HCWs were prospectively recruited within occupational safety and health measures and underwent a tuberculin skin test (TST) and the IGRA QuantiFERON®-TB Gold In-Tube (QFT-GIT) at baseline. The QFT-GIT was repeated 18 weeks later in the median. QFT-GIT conversions (and reversions) were defined as baseline IFN-γ < 0.35 IU/ml and follow-up IFN-γ ≥ 0.35 IU/ml (and vice versa). Predictors of persistently positive QFT-GIT results were calculated by logistic regression analysis. Results In total, 18 (9.9%) and 15 (8.2%) of 182 analyzed HCWs were QFT-GIT-positive at baseline and at follow-up, respectively. We observed a strong overall agreement between baseline and follow-up QFT-GIT results (κ = 0.70). Reversions (6/18, 33.3%) occurred more frequently than conversions (3/162, 1.9%). Age and positive prior and recent TST results independently predicted persistent QFT-GIT positivity. Furthermore, the chance of having persistently positive QFT-GIT results raised about 3% with each additional 0.1 IU/ml increase in the baseline IFN-γ response (adjusted odds ratio 1.03, 95% confidence interval 1.01-1.04). No active TB cases were detected within an observational period of more than two years. Conclusions The QFT-GIT's utility for the application in serial testing was limited by a substantial proportion of reversions. This shortcoming could be overcome by the implementation of a borderline zone for the interpretation of QFT-GIT results. However, further studies are needed to clearly define the within-subject variability of the QFT-GIT and to confirm that increasing age, concordantly positive TST results, and the extend of baseline IFN-γ responses may predict the persistence of QFT-GIT positivity over time in serially tested HCWs with only a low or medium TB screening risk in a TB low-incidence setting.

Abstract Background Tuberculous spondylitis (Pott's disease) is an ancient human disease. Because it is rare in high-income, tuberculosis (TB) low incidence countries, misdiagnoses occur as sufficient clinical experience is lacking. Case presentation We describe a fatal case of a patient with spinal TB, who was mistakenly irradiated for suspected metastatic lung cancer of the spine in the presence of a solitary pulmonary nodule of the left upper lobe. Subsequently, the patient progressed to central nervous system TB, and finally, disseminated TB before the accurate diagnosis was established. Isolation and antimycobacterial chemotherapy were initiated after an in-hospital course of approximately three months including numerous health care related contacts and procedures. Conclusion The rapid diagnosis of spinal TB demands a high index of suspicion and expertise regarding the appropriate diagnostic procedures. Due to the devastating consequences of a missed diagnosis, Mycobacterium tuberculosis should be considered early in every case of spondylitis, intraspinal or paravertebral abscess. The presence of certain alarm signals like a prolonged history of progressive back pain, constitutional symptoms or pulmonary nodules on a chest radiograph, particularly in the upper lobes, may guide the clinical suspicion.

Abstract Human polyomaviruses are known to cause persistent or latent infections, which are reactivated under immunosuppression. Polyomaviruses have been found to immortalize cell lines and to possess oncogenic properties. Moreover, the recently discovered Merkel cell polyomavirus shows a strong association with human Merkel cell carcinomas. Another novel human polyomavirus, WU polyomavirus (WUPyV), has been identified in respiratory specimens from patients with acute respiratory tract infections (ARTI). WUPyV has been proposed to be a pathogen in ARTI in early life and immunocompromised individuals, but so far its role as a causative agent of respiratory disease remains controversial. The objective of our study was to determine the prevalence of WUPyV infections in adult hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and to establish its potential clinical relevance by comparison to patients with stable COPD hospitalized for other reasons than acute exacerbation of COPD (AE-COPD). A total of 378 respiratory specimens, each 189 induced sputum and nasal lavage samples from 189 patients, who had been recruited in a prospective 2:1 ratio case-control set-up between 1999 and 2003, were evaluated for the presence of WUPyV DNA by real-time PCR. In the present study we could not detect WUPyV DNA in 378 respiratory specimens from 189 adult hospitalized patients with AE-COPD and stable COPD in four consecutive years. Persistence of viral replication or reactivation of latent WUPyV infection did not occur. WUPyV may not play a major role in adult immunocompetent patients with AE-COPD and stable COPD.

Abstract Background Smear-negative pulmonary tuberculosis (TB) accounts for a considerable proportion of TB transmission, which especially endangers health care workers (HCW). Novel Mycobacterium-tuberculosis-specific interferon-γ release assays (IGRAs) may offer the chance to define the burden of TB in HCW more accurately than the Mantoux tuberculin skin test (TST), but the data that is available regarding their performance in tracing smear-negative TB in the low-incidence, in-hospital setting, is limited. We conducted a large-scale, in-hospital contact investigation among HCW of a German university hospital after exposure to a single case of extensive smear-negative, culture-positive TB with pulmonary involvement. The objective of the present study was to evaluate an IGRA in comparison to the TST and to identify risk factors for test positivity. Methods Contacts were prospectively enrolled, evaluated using a standardized questionnaire, the IGRA QuantiFERON®-TB Gold in Tube (QFT-GIT) and the TST, and followed-up for two years. Active TB was ruled out by chest x-ray in QFT-GIT-positive subjects. Independent predictors of test positivity were established through the use of logistic regression analysis. Results Out of the 143 subjects analyzed, 82 (57.3%) had close contact, but only four (2.8%) experienced cumulative exposure to the index case >40 hours. QFT-GIT results were positive in 13 subjects (9.1%), while TST results were positive in 40 subjects (28.0%) at an induration >5 mm. Overall agreement was poor between both tests (kappa = 0.15). Age was the only predictor of QFT-GIT-positivity (Odds ratio 2.7, 95% confidence interval 1.32–5.46), while TST-positivity was significantly related to Bacillus Calmette-Guérin vaccination and foreign origin. Logistic regression analysis showed no relation between test results and exposure. No secondary cases of active TB were detected over an observational period of two years. Conclusion Our findings suggest a low contagiosity of the particular index case. The frequency of positive QFT-GIT results may in fact reflect the pre-existing prevalence of latent TB infection among the study population. TB transmission seems unlikely and contact tracing not generally warranted after cumulative exposure

Abstract Background For allergic disorders, the increasing prevalence over the past decade has been attributed in part to the lack of microbial burden in developed countries ('hygiene hypothesis'). Variation in genes encoding toll-like receptors (TLRs) as the receptor system for the first innate immune response to microbial stimuli has been implicated in various inflammatory diseases. We evaluated here the role of a coding variation, Ser249Pro, in the TLR6 gene in the pathogenesis of asthma, atopic dermatitis (AD) and chronic obstructive pulmonary disease (COPD). Methods Genotyping of the Ser249Pro polymorphism in 68 unrelated adult patients and 132 unrelated children with asthma, 185 unrelated patients with COPD, 295 unrelated individuals with AD and 212 healthy control subjects was performed by restriction enzyme digestion. Results We found a weak association of the 249Ser allele with childhood asthma (p = 0.03). Yet, significance was lost after Bonferroni correction. No association was evident for AD or COPD. Conclusion Variation in TLR6 might play a role in the pathogenesis of childhood asthma.

Background: Miners are at particular risk for tuberculosis (TB) infection due to exposure to silica dust and silicosis. The objectives of the present observational cohort study were to determine the prevalence of latent TB infection (LTBI) among aged German underground hard coal miners with silicosis or chronic obstructive pulmonary disease (COPD) using two commercial interferon-gamma release assays (IGRAs) and to compare their performance with respect to predictors of test positivity., Methods: Between October 2008 and June 2010, miners were consecutively recruited when routinely attending pneumoconiosis clinics for an expert opinion. Both IGRAs, the QuantiFERON®-TB Gold In-Tube (QFT) and the T-SPOT®.TB (T-SPOT), were performed at baseline. A standardized clinical interview was conducted at baseline and at follow-up. The cohort was prospectively followed regarding the development of active TB for at least two years after inclusion of the last study subject. Independent predictors of IGRA positivity were calculated using logistic regression., Results: Among 118 subjects (mean age 75 years), none reported recent exposure to TB. Overall, the QFT and the T-SPOT yielded similarly high rates of positive results (QFT: 46.6%; 95% confidence interval 37.6-55.6%; T-SPOT: 61.0%; 95% confidence interval 52.2-69.8%). Positive results were independently predicted by age ≥80 years and foreign country of birth for both IGRAs. In addition, radiological evidence of prior healed TB increased the chance of a positive QFT result fivefold. While 28 subjects were lost to follow-up, no cases of active TB occurred among 90 subjects during an average follow-up of >2 years., Conclusions: Considering the high prevalence of LTBI, the absence of recent TB exposure, and the currently low TB incidence in Germany, our study provides evidence for the persistence of specific interferon-gamma responses even decades after putative exposure. However, the clinical value of current IGRAs among our study population, although probably limited, remains uncertain.

Gamma interferon (IFN-γ) release assays (IGRAs) are used increasingly for the periodic tuberculosis (TB) screening of health care workers (HCWs), although data regarding the reproducibility and interpretation of serial testing results in countries with a low incidence of TB are scarce. The present study evaluated and compared the within-subject variability of dichotomous and continuous results of two commercial IGRAs, the QuantiFERON-TB Gold In-Tube (QFT) and the T-SPOT.TB (T-SPOT), in German HCWs during a 4-week period. Thirty-five immunocompetent HCWs with low or medium TB screening risk and without known recent TB exposure or tuberculin skin test application were tested repeatedly with both IGRAs at weekly intervals. A total of 158 valid results were obtained for each IGRA. Changes of about ±70% (QFT) and ±60% (T-SPOT) from the mean IFN-γ response accounted for 95% of the within-subject variability. However, according to the manufacturers' cutoffs, inconsistent results were observed more frequently for the QFT (28.6%; four conversions, six reversions) than for the T-SPOT (8.6%; three reversions; P < 0.001). The overall agreement between the IGRAs was good. Regression toward the means accounted for a significant decline in mean IFN-γ responses of about 25% between successive visits for both IGRAs. Although both assays were highly reliable and reproducible, we observed substantial within-subject variability and regression toward the means during a 4-week period, which should be considered when interpreting serial testing results in comparable populations and settings. Our data support the use of borderline zones for the interpretation of serial IGRA results and the retesting of borderline positive results before offering preventive chemotherapy.

Objective: Human bocavirus (HBoV) is a recently discovered parvovirus associated with acute respiratory tract infections in children. The objective of the present study was to determine the frequency and clinical relevance of HBoV infection in adult patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD)., Methods: We retrospectively tested 212 COPD patients, 141 (66.5%) with AE-COPD and 71 (33.5%) with stable disease, of whom nasal lavage and induced sputum had been obtained for the presence of HBoV deoxyribonucleic acid (DNA). The specificity of positive polymerase chain reaction results was confirmed by sequencing., Results: Two hundred two of 212 patients for whom PCR results were available both for nasal lavage and induced sputum samples were eligible for data analysis. HBoV DNA was detected in three patients (1.5%). Of those, only one patient had AE-COPD. Thus, the frequency of HBoV infection demonstrated to be low in both AE-COPD (0.8%) and stable COPD (2.9%). HBoV was found in two sputum and one nasal lavage sample in different patients, respectively. Sequencing revealed >99% sequence identity with the reference strain., Conclusion: HBoV detection was infrequent. Since we detected HBoV in both upper and lower respiratory tract specimens and in AE-COPD as well as stable disease, a major role of HBoV infection in adults with AE-COPD is unlikely.

Bacterial infection and colonization plays an important role in COPD. The inflammatory response to these bacteria is mediated by Toll-like receptors. The Asp299Gly polymorphism of the Toll-like receptor-4 (TLR4) has been shown to be associated with decreased lipopolysaccharide (LPS) signal transduction resulting in impaired antimicrobial defense. Because altered TLR4 signalling may facilitate bacterial infection, we clinically phenotyped and genotyped 152 patients with COPD (including 24 non-smokers), and 444 healthy controls for the presence of the Asp299Gly polymorphism. Frequencies of the TLR4 Gly allele (4% vs. 8% in controls, odds ratio (OR) 2.24 (95% confidence interval (95%CI) 1.17-4.3)) as well as TLR4 Gly genotype (6% vs. 13% in controls, OR 2.39 (95%CI 1.20-4.79)) were significantly decreased among the patients with COPD. The TLR4 Gly allele was not detected at all in a subgroup of non-smoking patients (n=24). We conclude that the frequency of the Asp299Gly polymorphism is decreased in COPD patients. Unaltered LPS signal transduction by TLR4 may be important for the development of COPD.

Patients with obstructive sleep apnoea syndrome (OSAS) have an increased car accident rate. Investigations on accident frequency are based on case history, insurance reports and driving simulator studies. The present study combines neuropsychological testing of different attention aspects engaged in driving a car and driving simulation to evaluate a suitable instrument for assessing therapeutic effects of continuous positive airway pressure (CPAP). Driving simulator investigation and neuropsychological testing of alertness, vigilance and divided attention were performed in 31 patients with polysomnographically confirmed OSAS (apnoea-hypopnoea index 24.8+/-21.5.h(-1)) before, and 2 and 42 days after initiation of CPAP. Divided attention and alertness improved significantly during CPAP, whereas vigilance remained unchanged. However, accident frequency (OSAS before therapy: 2.7+/-2.0; 2 days after CPAP: 1.5+/-1.4; 42 days after CPAP: 0.9+/-1.3) and frequency of concentration faults (OSAS before therapy: 12.4+/-5.1; 2 days after CPAP: 6.5+/-3.9; 42 days after CPAP: 4.9+/-3.3) decreased in the simulated driving situation after 2 and 42 days of therapy. There was no relation between accident frequency, concentration faults and daytime sleepiness, as measured by the Epworth Sleepiness Scale, and polysomnographic or neuropsychological findings, respectively. In conclusion, the present results suggest that driving simulation is a possible benchmark parameter of driving performance in obstructive sleep apnoea syndrome patients.

One year after the first outbreak infections with SARS associated coronavirus were again reported and the clinical picture varied. Because health care facilities will have to initiate immediate preventive action in cases of probable SARS we tested the potential of PCR to exclude SARS associated coronavirus in patients hospitalized with respiratory symptoms. Based on primers published recently a real time Taqman PCR was established and evaluated. Lower respiratory tract specimens of patients with acute exacerbation of COPD were investigated. 141 patients with mild to moderate COPD were included. The assay was specific, sensitive, precise and reproducible and allowed absolute quantification without cross-reactivity to other respiratory viruses. None of the samples were positive for SARS associated coronavirus. Our RT-PCR for SARS associated coronavirus is a valid and practicable method to further exclude SARS in X-ray negative patients with respiratory symptoms, even in the presence of other respiratory RNA viruses.

Recent evidence suggests that Staphylococcus aureus enterotoxins (SAEs) could modify airway disease by acting as superantigens, an immune response that can be monitored by detection of IgE antibodies to SAEs. We studied the expression of total IgE and specific IgE to SAEs using the Uni-CAP system in healthy controls, smokers without COPD and COPD patients. Only 1/10 controls (10%) and 1/16 smokers (6.3%) had IgE to SAEs compared to 7/18 patients with stable COPD (38.9%) and 21/54 patients with exacerbated COPD (38.9%). The IgE levels to SAEs of the patients with stable COPD (0.18 [0.05-26.2]kUA/l) and the patients with exacerbated COPD (0.09 [0.05-18.6]kUA/l) were significantly higher than those of smokers (n = 16; 0.05 [0.05-0.82]kUA/l) and controls (n = 11; 0.05 [0.05 0.9]kUA/l, P<0.05). IgE to SAEs decreased significantly in the exacerbated patients during hospitalization (0.13 [0.05-18.3] vs. 0.05 [0.05-11]kUA/l, P<0.001) going along with a significant increase in FEV1 (38.1 [16.9-79.5] vs. 51.6 [15-80]%predicted, P<0.001). Similarly to severe asthma, we found significantly elevated IgE to SAE in COPD patients. Our data for the first time suggest differences between healthy subjects, smokers and patients with established COPD regarding the role of bacterial products and point to a possible disease modifying role of SAEs.

T-cell-derived cytokines have been implicated in the pathogenesis of asthma and it has been suggested that Th2-type cytokines (interleukin-4 [IL-4], interleukin-5 [IL-5]) are pivotal in the allergic inflammation. However, there are little data on human cytokine production by individual T cells at the protein level, in particular in asthmatic children. In this study we analyzed the cytokine production at the single cell level in peripheral blood from mild atopic asthmatic (AA) children and adults and age-matched atopic nonasthmatic (AN) and nonatopic nonasthmatic (NN) control subjects (n = 9 in each group) using the technique of intracellular cytokine detection by flow cytometry. Comparing asthmatic children with atopic and nonatopic control subjects, an increased percentage of IL-5-producing T cells (AA: median 4.9% [range 1.1 to 8.9%]; AN: 0.3% [0.2 to 0.9%], p = 0.003; NN: 0.4% [0.1 to 3.8%], p = 0.001) was detectable, with a positive correlation to the number of peripheral eosinophils and to bronchial hyperresponsiveness. The frequency of IL-4-producing T cells was increased in both atopic groups compared with nonatopic controls (AA: 1.2% [0.2 to 2.6%], p = 0.011; AN: 0.8% [0.4 to 3.7%], p = 0.007; NN: 0.4% [0.2 to 0.9%]) with a positive correlation to total IgE concentration. In adults there were no differences in IL-5- or IL-4-producing T cells between all three groups. A substantial proportion of T cells coproducing IL-4 and IL-5 was not detectable in children and adults. These findings indicate that in asthmatic children the frequencies of Th2-type-producing T cells are increased and that expression of IL-4 and IL-5 is regulated independently.

Occupational asthma due to platinum salts is a frequent disease in platinum refineries. The diagnosis is based upon a history of work related symptoms and a positive skin prick test with platinum salts. Bronchial provocation tests have not been performed in epidemiological studies because the skin test is believed to be highly specific and sensitive. As no reliable data about this issue currently exist, this study assesses the use of skin prick and bronchial provocation tests with methacholine and platinum salt in platinum refinery workers. Twenty seven of 35 workers, who were referred to our clinic with work related symptoms and nine control subjects with bronchial hyperreactivity underwent a skin prick test and bronchial provocation with methacholine and platinum salt. For skin prick and bronchial provocation tests with platinum salt a 10(-2)-10(-8) mol/l hexachloroplatinic acid solution, in 10-fold dilutions was used. Four of the 27 subjects and all controls showed neither a bronchial reaction nor a skin reaction. Twenty three subjects were considered allergic to platinum salt; 22 of these showed a fall of 50% or more in specific airway conductance after inhalation of the platinum salt solution. Four workers experienced a positive bronchial reaction despite a negative skin prick test. No correlation of responsiveness to methacholine with responsiveness to platinum salt was found, but the skin prick test correlated with the bronchial reaction to platinum salt (rs = 0.50, p less than 0.023, n = 22). One dual reaction was seen in bronchial provocation tests. Side effects of both skin tests and bronchial provocation tests with platinum salt were rare and were not encountered in workers without a skin reaction to platinum salt. It is concluded that bronchial provocation tests with platinum salts should be performed on workers with work related symptoms but negative skin tests with platinum salts.

In 10 patients with precapillary pulmonary hypertension due to pulmonary fibrosis, the arterial blood pressure, right heart hemodynamics, cardiac output, and arterial oxygen partial pressure were measured to evaluate the benefits of acute sublingual (5 mg) nitrendipine. Additionally, the effect of oxygen enriched air was compared to control. At rest, nitrendipine significantly diminished arterial blood pressure [102 +/- 3 to 93 +/- 3 mm Hg (mean +/- SEM)], right atrial pressure (5.7 +/- 0.9 to 3.4 +/- 0.8 mm Hg), mean pulmonary artery pressure (33.4 +/- 3.5 to 29.8 +/- 3.3 mm Hg), and pulmonary artery wedge pressure (13.0 +/- 2.0 to 6.8 +/- 0.8 mm Hg). During exercise, nitrendipine reduced mean pulmonary artery pressure (54.5 +/- 4.8 to 49.3 +/- 4.7 mm Hg) and right atrial pressure (9.3 +/- 1.3 to 6.8 +/- 1.4 mm Hg). A diminuation of arterial partial oxygen pressure did not occur at rest (63.2 +/- 3.8 mm Hg) or during exercise (50.9 +/- 5.1 mm Hg). Thus, nitrendipine causes a slight but significant improvement of right heart hemodynamics. The occurrence of arteriovenous intrapulmonary shunting due to vasodilatating effects of nitrendipine can be excluded. Also, nitrendipine can safely be used in combined arterial hypertension and pulmonary fibrosis.