Autoadjusted versus fixed CPAP for obstructive sleep apnoea: a multicentre, randomised equivalence trial.

BACKGROUND: The obstructive sleep apnoea syndrome (OSAS) is conventionally treated by continuous positive airway pressure set at a fixed level (fCPAP). Automatic mask pressure adjustment (autoCPAP) is increasingly used during home therapy. We investigated whether autoCPAP is equivalent to fCPAP in improving sleepiness in patients with OSAS in the long-term. METHODS: In this multicentre equivalence trial, 208 patients with OSAS, with median Epworth sleepiness score (ESS) 13, apnoea/hypopnoea index 48.4/hour, were randomised to treatment with autoCPAP (5-15 mbar) or fCPAP (pressure set at the 90th percentile applied by autoCPAP during 2-4 weeks adaptation). Coprimary outcomes were changes in subjective and objective sleepiness from baseline to 2 years after treatment. Equivalence ranges were ±2 points in ESS and ±3 min sleep resistance time evaluated by recording responses to light signals. RESULTS: At 2 years, in the intention to treat analysis, the reduction in sleepiness versus pretreatment baseline was similar in patients using autoCPAP (n=113, mean ESS-change -6.3, 95% CI -7.1 to -5.5; sleep resistance time +8.3 min, +6.9 to +9.7) and fCPAP (n=95, mean ESS-change -6.2, 95% CI -7.0 to -5.3; sleep resistance time +6.3 min, +4.7 to +7.8). The 95% CI of difference in ESS-reduction between autoCPAP and fCPAP was -0.9 to +1.4 and the 95% CI of difference in increase in sleep resistance time was -2.6 to +1.0 min. Blood pressure reduction and OSAS-related costs were similar between groups. CONCLUSIONS: AutoCPAP and fCPAP are equivalent within prespecified ranges in improving subjective and objective sleepiness in patients with OSAS over the course of 2 years. Costs of these treatments are similar. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00280800.

Effect of rituximab on pulmonary function in patients with rheumatoid arthritis.

BACKGROUND: Rituximab (RTX), a B-cell depleting monoclonal antibody is increasingly used in several antibody-mediated diseases. It has been reported to cause pulmonary toxicity, though mainly during polychemotherapy of malignant lymphoma. Prospective data on RTX-induced pulmonary complications in patients with rheumatoid arthritis (RA) are lacking. METHODS AND METHODS: Serial spirometries and measurements of diffusion capacity of the lung for carbon monoxide (DLCO) in patients with RA before and 2, 4, 8, and 26 weeks after treatment with RTX were performed. A reduction from baseline of forced vital capacity (FVC) of ≥10%, or ≥15% of DLCO was defined as indicative for pulmonary toxicity. RESULTS: Thirty-three patients (mean (SD) age 59 (12) years, 27% males) were included. Mean (SD) FVC predicted and DLCO predicted at baseline were 108% (18%) and 88% (18%), respectively. In contrast to FVC, DLCO showed a progressive decline during follow-up with a maximum reduction of 6.1% (95%CI 2.5%, 9.7%; p = 0.001) at 26 weeks compared with baseline. After 26 weeks, 22% of the patients had a ≥15% DLCO decline. None of the patients reported increased dyspnea during follow-up. Risk factors for pulmonary function changes after treatment with RTX were cigarette smoking, repeated administration of the drug, and co-medication with Prednisone. CONCLUSION: Although no cases of symptomatic lung injury were observed, the progressive DLCO decline seems to indicate the presence of subclinical RTX-induced pulmonary toxicity.

Causal and synthetic associations of variants in the SERPINA gene cluster with alpha1-antitrypsin serum levels.

Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD). The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood. We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort. Five common SNPs, defined by showing minor allele frequencies (MAFs) >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of ß = -0.068 g/L per minor allele (P = 1.20*10(-12)). But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis, as well as exon-sequencing in a subsample (N = 410), suggested that AAT serum level is causally determined at this locus by rare (MAF<1%) and low-frequent (MAF 1-5%) variants only, in particular by the well-documented protein inhibitor S and Z (PI S, PI Z) variants. Replication of the association of rs4905179 with AAT serum levels in the Copenhagen City Heart Study (N = 8273) was successful (P<0.0001), as was the replication of its synthetic nature (the effect disappeared after adjusting for PI S and Z, P = 0.57). Extending the analysis to lung function revealed a more complex situation. Only in individuals with severely compromised pulmonary health (N = 397), associations of common SNPs at this locus with lung function were driven by rarer PI S or Z variants. Overall, our meta-analysis of lung function in ever-smokers does not support a functional role of common SNPs in the SERPINA gene cluster in the general population.

Determinants of endothelial function in patients with COPD.

Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular mortality. Endothelial dysfunction may underpin this association. This cross-sectional study aimed to determine the impact of airflow obstruction, systemic inflammation, oxidative stress, sympathetic activation, hypoxaemia and physical activity on endothelial function in COPD. In stable COPD patients, assessments of endothelial function by flow-mediated dilatation (FMD), cardiovascular risk (Pocock score), airflow obstruction (forced expiratory volume in 1 s (FEV1)), systemic inflammation (high-sensitivity C-reactive protein and interleukin-6), oxidative stress (malondialdehyde), sympathetic activation (baroreflex sensitivity), hypoxaemia (arterial oxygen tension), hypercapnia (arterial carbon dioxide tension (PaCO2)), physical activity (steps per day) and exercise capacity (6-min walking distance) were performed. Associations between FMD and potential determinants were assessed in univariate and multivariate analyses. 106 patients (Global Initiative for Chronic Obstructive Lung Disease stage I/II 35%, stage III 25% and stage IV 40%) were included. In multivariate analysis FEV1 was positively associated with FMD, independent of other significant FMD determinants from univariate analysis (sex, smoking, combined inhaled long-acting ß-adrenergic and steroid medication, heart rate, baroreflex sensitivity and PaCO2) and adjusted for potential confounders (cardiovascular risk and age). In addition, the FMD and FEV1 association was modified by physical activity. The findings of this study demonstrate that the severity of airflow obstruction is a significant determinant of endothelial function in patients with COPD. A high level of physical activity seems to have a favourable effect on this association.

Occupational exposure to dusts, gases, and fumes and incidence of chronic obstructive pulmonary disease in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults.

RATIONALE: There is limited evidence from population-based studies demonstrating incidence of spirometric-defined chronic obstructive pulmonary disease (COPD) in association with occupational exposures. OBJECTIVES: We evaluated the association between occupational exposures and incidence of COPD in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). MEASUREMENTS AND MAIN RESULTS: Prebronchodilator ratio of forced expiratory volume in 1 second over forced vital capacity (FEV(1)/FVC) was measured in 4,267 nonasthmatic SAPALDIA participants ages 18-62 at baseline in 1991 and at follow-up in 2001-2003. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion (FEV(1)/FVC < 0.70) and Quanjer reference equation (FEV(1)/FVC < lower limit of normal [LLN]), and categorized by severity (≥ 80% and <80% predicted FEV(1) for stage I and stage II+, respectively). Using a job-exposure matrix, self-reported occupations at baseline were assigned exposures to biological dusts, mineral dusts, gases/fumes, and vapors, gases, dusts, or fumes (VGDF) (high, low, or unexposed as reference). Adjusted incident rate ratios (IRRs) of stage I and stage II+ COPD were estimated in mixed Poisson regression models. Statistically significant (P < 0.05) IRRs of stage II+ GOLD and LLN-COPD, indicating risks between two- and fivefold, were observed for all occupational exposures at high levels. Occupational exposure-associated risk of stage II+ COPD was observed mainly in males and ages ≥ 40 years, and remained elevated when restricted to nonsmokers. CONCLUSIONS: In a Swiss working adult population, occupational exposures to biological dusts, mineral dusts, gases/fumes, and VGDF were associated with incidence of COPD of at least moderate severity.

Validation of a small cough detector.

Research question: The assessment of cough frequency in clinical practice relies predominantly on the patient's history. Currently, objective evaluation of cough is feasible with bulky equipment during a brief time (i.e. hours up to 1 day). Thus, monitoring of cough has been rarely performed outside clinical studies. We developed a small wearable cough detector (SIVA-P3) that uses deep neural networks for the automatic counting of coughs. This study examined the performance of the SIVA-P3 in an outpatient setting. Methods: We recorded cough epochs with SIVA-P3 over eight consecutive days in patients suffering from chronic cough. During the first 24 h, the detector was validated against cough events counted by trained human listeners. The wearing comfort and the device usage were assessed using a questionnaire. Results: In total, 27 participants (mean±sd age 50±14 years) with either chronic unexplained cough (n=12), COPD (n=4), asthma (n=5) or interstitial lung disease (n=6) were studied. During the daytime, the sensitivity of SIVA-P3 cough detection was 88.5±2.49% and the specificity was 99.97±0.01%. During the night-time, the sensitivity was 84.15±5.04% and the specificity was 99.97±0.02%. The wearing comfort and usage of the device was rated as very high by most participants. Conclusion: SIVA-P3 enables automatic continuous cough monitoring in an outpatient setting for objective assessment of cough over days and weeks. It shows comparable sensitivity or higher sensitivity than other devices with fully automatic cough counting. Thanks to its wearing comfort and the high performance for cough detection, it has the potential for being used in routine clinical practice.

Serum levels and genotype distribution of α1-antitrypsin in the general population.

RATIONALE: α1-Antitrypsin (AAT) deficiency is one of the commonest rare respiratory disorders worldwide. Diagnosis, assessment of risk for developing chronic obstructive pulmonary disease (COPD), and management of replacement therapy require the availability of precise and updated ranges for protein serum levels. OBJECTIVE: This paper aims to provide ranges of serum AAT according to the main genotype classes in the general population. METHODS: The authors correlated mean AAT serum levels with the main SERPINA1 variants (M1Ala/M1Val (rs6647), M3 (rs1303), M2/M4 (rs709932), S (rs17580) and Z (rs28929474)) in 6057 individuals enrolled in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) cohort. RESULTS: The following ranges (5th-95th percentile) of AAT were found in the serum (g/litre): 1.050-1.640 for PI*MM, 0.880-1.369 for PI*MS, 0.730-1.060 for PI*SS, 0.660-0.997 for PI*MZ and 0.490-0.660 for PI*SZ. There was very little overlap in AAT serum levels between genotype classes generally not believed to confer an enhanced health risk (MM and MS) and those associated with an intermediate AAT deficiency and a potentially mildly enhanced health risk (SS, MZ). CONCLUSION: This work resulted in three important findings: technically updated and narrower serum ranges for AAT according to PI genotype; a suggestion for a population-based 'protective threshold' of AAT serum level, used in decision-making for replacement therapy; and more precise ranges framing the intermediate AAT deficiency area, a potential target for future primary prevention.

Randomised controlled trial for emphysema with a selective agonist of the γ-type retinoic acid receptor.

Palovarotene is an oral γ-selective retinoid agonist. In animal emphysema models, palovarotene reduced inflammation, promoted structural repair and functional improvement. REPAIR (Retinoid treatment of Emphysema in Patients on the α(1)-antitrypsin International Registry), was an investigator-initiated, double-blind, placebo-controlled randomised study to assess the safety and efficacy of 5 mg·day(-1) palovarotene given for 1 year to 262 patients with severe α(1)-antitrypsin deficiency and emphysema confirmed by computed tomography. Change in volume-adjusted 15th percentile point lung density from baseline in 1 year was the primary end-point; functional end-points were also regularly assessed. We randomly assigned 133 and 129 patients to placebo or palovarotene, respectively. Both groups were well matched for all baseline characteristics, including respiratory medications. 88% and 85% of patients completed 1 year of treatment with placebo and palovarotene, respectively. Palovarotene was generally well tolerated. In the study completers population, the placebo-corrected difference of lung density was -0.45 HU at week 28 (p=0.64) and -0.25 HU at week 52 (p=0.94). A nonsignificant treatment difference in most functional parameters of the lung in favour of the drug was observed over time suggesting potential pharmacological effects of palovarotene. Palovarotene 5 mg·day(-1) over 1 yr failed to show a significant benefit on lung density in moderate-to-severe emphysema secondary to severe α(1)-antitrypsin deficiency.

Low-dose CT of the lung: potential value of iterative reconstructions.

OBJECTIVES: To prospectively assess the impact of sinogram-affirmed iterative reconstruction (SAFIRE) on image quality of nonenhanced low-dose lung CT as compared to filtered back projection (FBP). METHODS: Nonenhanced low-dose chest CT (tube current-time product: 30 mAs) was performed on 30 patients at 100 kVp and on 30 patients at 80 kVp. Images were reconstructed with FBP and SAFIRE. Two blinded, independent readers measured image noise; two readers assessed image quality of normal anatomic lung structures on a five-point scale. Radiation dose parameters were recorded. RESULTS: Image noise in datasets reconstructed with FBP (57.4 ± 15.9) was significantly higher than with SAFIRE (31.7 ± 9.8, P < 0.001). Image quality was significantly superior with SAFIRE than with FBP (P < 0.01), without significant difference between FBP at 100 kVp and SAFIRE at 80 kVp (P = 0.68). Diagnostic image quality was present with FBP in 96% of images at 100 kVp and 88% at 80 kVp, and with SAFIRE in 100% at 100 kVp and 98% at 80 kVp. There were significantly more datasets with diagnostic image quality with SAFIRE than with FBP (P < 0.01). Mean CTDI(vol) and effective doses were 1.5 ± 0.7 mGy·cm and 0.7 ± 0.2 mSv at 100 kVp, and 1.4 ± 2.8 mGy · cm and 0.5 ± 0.2 mSv at 80 kVp (P < 0.001, both). CONCLUSIONS: Use of SAFIRE in low-dose lung CT reduces noise, improves image quality, and renders more studies diagnostic as compared to FBP. KEY POINTS: Low-dose computed tomography is an important thoracic investigation tool. Radiation dose can be less than 1 mSv with iterative reconstructions. Iterative reconstructions render more low-dose lung CTs diagnostic compared to conventional reconstructions.

The effects of controlled breathing during pulmonary rehabilitation in patients with COPD.

BACKGROUND: Conventional pulmonary rehabilitation programs improve exercise tolerance but have no effect on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). The role of controlled breathing using respiratory biofeedback during rehabilitation of patients with COPD remains unclear. OBJECTIVES: To compare the effects of a conventional 4-week pulmonary rehabilitation program with those of rehabilitation plus controlled breathing interventions. METHODS: A randomized controlled trial was performed. Pulmonary function (FEV1), exercise capacity (6-min walking distance, 6 MWD), health-related quality of life (chronic respiratory questionnaire, CRQ) and cardiac autonomic function (rMSSD) were evaluated. RESULTS: Forty COPD patients (mean±SD age 66.1±6.4, FEV1 45.9±17.4% predicted) were randomized to rehabilitation (n=20) or rehabilitation plus controlled breathing (n=20). There were no statistically significant differences between the two groups regarding the change in FEV1 (mean difference -0.8% predicted, 95% CI -4.4 to 2.9% predicted, p=0.33), 6 MWD (mean difference 12.2 m, 95% CI -37.4 to 12.2 m, p=0.16), CRQ (mean difference in total score 0.2, 95% CI -0.1 to 0.4, p=0.11) and rMSSD (mean difference 2.2 ms, 95% CI -20.8 to 25.1 ms, p=0.51). CONCLUSIONS: In patients with COPD undergoing a pulmonary rehabilitation program, controlled breathing using respiratory biofeedback has no effect on exercise capacity, pulmonary function, quality of life or cardiac autonomic function.

Effects of continuous positive airway pressure therapy withdrawal in patients with obstructive sleep apnea: a randomized controlled trial.

RATIONALE: To establish a new approach to investigate the physiological effects of obstructive sleep apnea (OSA), and to evaluate novel treatments, during a period of continuous positive airway pressure (CPAP) withdrawal. OBJECTIVES: To determine the effects of CPAP withdrawal. METHODS: Forty-one patients with OSA and receiving CPAP were randomized to either CPAP withdrawal (subtherapeutic CPAP), or continued CPAP, for 2 weeks. Polysomnography, sleepiness, psychomotor performance, endothelial function, blood pressure (BP), heart rate (HR), urinary catecholamines, blood markers of systemic inflammation, and metabolism were assessed. MEASUREMENTS AND MAIN RESULTS: CPAP withdrawal led to a recurrence of OSA within a few days and a return of subjective sleepiness, but was not associated with significant deterioration of psychomotor performance within 2 weeks. Endothelial function, assessed by flow-mediated dilatation, decreased significantly in the CPAP withdrawal group compared with therapeutic CPAP (mean difference in change, -3.2%; 95% confidence interval [CI], -4.5, -1.9%; P < 0.001). Compared with continuing CPAP, 2 weeks of CPAP withdrawal was associated with a significant increase in morning systolic BP (mean difference in change, +8.5 mm Hg; 95% CI, +1.7, +15.3 mm Hg; P = 0.016), morning diastolic BP (mean difference in change, +6.9 mm Hg; 95% CI, +1.9, +11.9 mm Hg; P = 0.008), and morning HR (mean difference in change, +6.3 bpm, 95% CI, +0.4, +12.2 bpm; P = 0.035). CPAP withdrawal was associated with an increase in urinary catecholamines but did not lead to an increase in markers of systemic inflammation, insulin resistance, or blood lipids. CONCLUSIONS: CPAP withdrawal usually leads to a rapid recurrence of OSA, a return of subjective sleepiness, and is associated with impaired endothelial function, increased urinary catecholamines, blood pressure, and heart rate. Thus the proposed study model appears to be suitable to evaluate physiological and therapeutic effects in OSA. Clinical trial registered with www.controlled-trials.com (ISRCTN93153804).

Cardiac autonomic function and cardiovascular response to exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with impaired exercise tolerance, but it has not been established to what extent cardiac autonomic function impacts on exercise capacity. OBJECTIVE: To evaluate whether there is an association between airflow limitation and cardiac autonomic function and whether cardiac autonomic function plays a role in exercise intolerance and daily physical activity (PA) in patients with COPD. METHODS: Univariate and multivariate analyses were performed to evaluate the association between both 6-minute walking test (6MWT) and PA (steps per day) and pulmonary function, cardiac autonomic function (HR at rest, HRR and heart rate variability, HRV) in patients with COPD. RESULTS: In 154 COPD patients (87 females, mean [SD]: age 62.5 [10.7] years, FEV(1) %predicted (43.0 [19.2]%), mean HR at rest was elevated (86.4 [16.4] beats/min) and HRV was reduced (33.69 [28.96] ms) compared to published control data. There was a significant correlation between FEV(1) and HR at rest (r = -0.32, p < 0.001), between HR at rest and 6MWD (r = -0.26, p = 0.001) and between HR at rest and PA (r = -0.29, p = 0.010). No correlation was found between HRV and 6MWD (r = 0.089, p = 0.262) and PA (r = 0.075, p = 0.322). In multivariate analysis both HR and FEV(1) were independent predictors of exercise capacity in patients with COPD. CONCLUSIONS: In patients with COPD the degree of airflow limitation is associated with HR at rest. The degree of airflow limitation and cardiac autonomic function, as quantified by HR at rest, are independently associated with exercise capacity in patients with COPD.

Main pulmonary artery diameter from attenuation correction CT scans in cardiac SPECT accurately predicts pulmonary hypertension.

OBJECTIVES: To establish the value of the main pulmonary artery (MPA) diameter assessed from unenhanced computer tomography (CT) scans used for attenuation correction (AC) of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to predict pulmonary hypertension (PHT). BACKGROUND: In contrast-enhanced chest CT scans an MPA diameter of 29 mm or greater is an established predictor of PHT. However, it is unknown, whether measurements from an unenhanced CT scan for AC may be used as predictor of PHT. METHODS: 100 patients underwent SPECT MPI for assessment of coronary artery disease. PHT was defined as a right ventriculo-atrial gradient of 30 mm Hg or greater by Doppler echocardiography. We compared MPA diameter from CT to SPECT findings (right ventricular hypertrophy/enlargement, septal wall motion abnormality/perfusion defect, and D-shape) to determine the best predictor of PHT. RESULTS: PHT was found in 37 patients. An MPA diameter of 30 mm or greater yielded a sensitivity, specificity, accuracy, positive, and negative predictive value of 78%, 91%, 86%, 83%, and 88%, respectively. This yielded an area under the ROC curve of 0.85. CONCLUSIONS: MPA diameter from low-dose unenhanced multi-slice CT reliably predicts PHT, providing an important added clinical value from AC for SPECT MPI.

Cardiac autonomic dysfunction and health-related quality of life in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: COPD is associated with impaired health-related quality of life (HRQL) and cardiac autonomic dysfunction. Data describing the association between these factors in patients with COPD are mostly lacking. The objective of this study was to evaluate whether there is an association between cardiac autonomic dysfunction and HRQL in COPD. METHODS: We studied 60 patients with COPD (37 women, mean (SD) age 65.20 (7.73) years, FEV(1) % pred. 46.58 (18.53) %) and measured HRQL, as assessed by the Chronic Respiratory Disease Questionnaire, and cardiac autonomic dysfunction, as assessed by heart rate variability (HRV). Analysis of HRV was performed using a Holter-ECG device during a recording period of 5 min. To evaluate a possible association between these factors, univariate and multivariate analyses were used. RESULTS: There was a significant correlation between Chronic Respiratory Disease Questionnaire total score and both variables of HRV reflecting parasympathetic tone; root mean square successive difference of RR intervals (rMSSD) (r = 0.34, P = 0.012) and the density of the beat-to-beat oscillation in the N-N interval of HRV in the high-frequency band (HF power) (r = 0.35, P = 0.01). In a multivariate analysis rMSSD was found to be independently associated with HRQL after correcting for FEV(1), carbon monoxide transfer coefficient (DL(CO)), 6MWD and CRP. CONCLUSIONS: Resting parasympathetic tone, as measured by HRV, is independently associated with HRQL, which emphasizes the role of cardiac autonomic dysfunction on HRQL in patients with COPD.

[Nontuberculous mycobacterial infections of the lung]. / Atypische Mykobakteriose der Lunge.

Nontuberculous mycobacterium (NTM) species are mycobacterial species other than those belonging to the Mycobacterium tuberculosis complex and M. leprae. NTM are generally free-living organisms that are ubiquitous in the environment. Pulmonary disease, especially in older persons with and without underlying lung disease, is caused primarily by M. avium complex (MAC) and M. kansasii. The symptoms and signs of MAC lung disease are variable and not specific, but include cough, malaise, weakness, dyspnoea, chest discomfort and occasionally hemoptoe. Two major clinical presentations include disease in those with underlying lung disease, primarily white, middle-aged or elderly men - often alcoholics and/or smokers with underlying chronic obstructive lung disease, patients in whom MAC develops in areas of prior bronchiectasis, and patients with cystic fibrosis; and those without known underlying lung disease, including non-smoking women over age 50 who have interstitial patterns on chest radiography. M. kansasii infections are endemic in cities with infected tap water. Symptoms of the M. kansasii lung disease resemble to tuberculosis. M. abszessus is the most pathogenic rapid growing Mycobacterium which causes pulmonary infection. The American Thoracic Society and Infectious Disease Society of America's diagnostic criteria for nontuberculous mycobacterial pulmonary infections include both imaging studies consistent with pulmonary disease and recurrent isolation of mycobacteria from sputum or isolated from at least one bronchial wash in a symptomatic patient. For treatment of MAC lung disease we recommend depending on severity and susceptibility testing a three to four drug treatment with a macrolide, rifampicin and ethambutol and for M. kansasii a treatment with Isoniazid, rifampicin and ethambutol. Surgical management only plays a role in rare and special cases. Treatment should be continued until sputum cultures are consecutively negative for at least one year.

Genetic polymorphisms of the serotonin transporter, but not the 2a receptor or nitric oxide synthetase, are associated with pulmonary hypertension in chronic obstructive pulmonary disease.

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 > or =25 mm Hg) was present in 55% and usually mild, but out of proportion (mPAP > or =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.

[Be cautious with a prognosis!]. / Vorsicht mit Prognosen!

A 37-years old patient of south Indian origin presented with pain in his right scapular region radiating to the right arm, numbness and muscular weakness of the fourth and fifth finger. Computed tomography (CT) revealed a mass at the right pleural dome with arrosion of the first rib (Pancoast presentation), an osteolytic process in the fourth rib and in the right hip. All three lesions had a high FDG uptake in the PET/CT suggestive for lung cancer metastases in this smoker. Surprisingly, the CT-guided fine needle biopsy revealed no malignancy, but granulomatous inflammation and epitheloid cells. Microscopy for acid-fast bacilli (AFB) was negative, but the culture was positive for AFB. The HIV-negative patient received a regular antituberculous chemotherapy. His condition as well as the radiological findings improved gradually. In the majority of cases, space occupying masses in the upper sulcus are caused by non-small cell lung cancers. Extrapulmonal tuberculosis infection presenting as a Pancoast syndrome is a curiosity. However, with respect to the patients ethnical background this diagnosis should have been considered earlier.

[Dyspnea - pathophysiology and differential diagnosis]. / Dyspnoe - Pathophysiologie und Differentialdiagnose.

Shortness of breath is a very common symptom and hence of interest for physicians of various specialities. Despite research including modern imaging methods the neurophysiology of dyspnea is still poorly understood. According to a frequently suggested theory, the basic mechanisms consist of a mismatch between efferent signals to the respiratory muscles and the afferent feedback from pulmonary and chest-wall receptors, which reflect the efficiency of innervation. A concept, useful in daily practice divides acute and chronic forms of dyspnea according to an increase need of breathing and/or an impaired organ function.

[Imaging of the chest]. / Bildgebung im Thoraxraum.

Imaging of the chest made considerable progress over the past twenty years. Nevertheless, a chest X-ray remains one of the most informative and hence frequently used diagnostic procedures in daily medical practice. The choice of additional imaging techniques has to be based on pertinent differential diagnostic considerations. Basic knowledge of the various radiological techniques facilitates and improves the diagnostic process and a common terminology enhances the communication between the clinician and the radiologist. Modern radiological procedures are less invasive as compared to some historical procedures, are well tolerated by the patients and have a high sensitivity and specificity.