Distribution of chronic cough phenotypes in the general population: A cross-sectional analysis of the LEAD cohort in Austria.

RATIONALE: Recent guidelines consider chronic cough to be a unique clinical entity with different phenotypes. We aimed to investigate them in a general population and to describe prevalence, distribution, and characteristics of these phenotypes within the Austrian general population. METHODS: From the LEAD study, a longitudinal observational population-based cohort, data from questionnaires and spirometry of 10,057 adult participants was analysed. Chronic cough was defined as coughing nearly every day during the last 12 months for at least 3 months (>12 weeks). RESULTS: The prevalence of chronic cough was 9% and increased with age. We found no sex predominance but a female preponderance (68%) in never smokers. A presumable cause was identified in 85% of which more than half (53.9%) had two phenotypes, 36.9% belonged to one only and 9.2% to three or more. Regarding the distribution of phenotypes, 40.8% were current smokers, 32.6% had an ACE inhibitor intake, 18.2% GERD, 17.6% asthmatic cough, 9.7% UACS and 28.3% other diseases associated with chronic cough. 15% had unexplained chronic cough with no identifiable phenotype. Current smoking, low socioeconomic status, obesity, COPD and obstructive sleep apnea were associated factors with chronic cough. CONCLUSION: Chronic cough is common among adults in Austria and highly prevalent in the older population. Most participants can be phenotyped with simple questionnaire-based assessment and can therefore potentially receive specific treatment without intensive clinical workup.

[The Austrian LEAD (Lung hEart sociAL boDy) Study: Background of the Austrian Longitudinal Cohort Study]. / The Austrian LEAD (Lung hEart sociAL boDy) Study: Die Hintergründe der österreichischen longitudinalen Kohortenstudie.

More research is needed to elucidate natural history and underlying pathomechanisms of the most common airway diseases, Asthma and COPD. In the last decade risk factors affecting the natural history of lung function, defined by the decline of lung function over time, have been evaluated. Moreover, scientific methods have been extended and novel biomarkers, genetics, metabolomics, and epidemiology are dominant tools for investigating the natural history of lung function and potential risk factors. Evidence shows that lung function in childhood is a predictor for lung function in adulthood and risk factors starting in utero contribute to lung function decline during life. Therefore, recently it has been hypothesized that COPD begins in childhood. Thus, prospective investigation of lung function changes including novel scientific methodology has been advocated. The Austrian LEAD  study has been initiated in the general population 2012 to investigate the natural history of obstructive airway diseases.

A case of tracheobronchial amyloidosis treated with endoscopic debulking and external beam radiation therapy.

We report on a 55-year-old patient who was admitted to hospital because of recurrent pneumonia. CT imaging provided airway narrowing and mural thickening of the distal trachea and mainstem bronchi, compatible with endobronchial polypoid, toric-shaped changes of the distal tracheal wall spreading into both the left and right bronchial system. Bronchoscopy was performed and biopsies revealed the diagnosis of tracheobronchial amyloidosis. We performed a combination of bronchoscopic debulking and consecutive external beam radiation therapy with the result of no further progression of the disease, stable endobronchial situation, and functional improvements at a follow up at 6 months.

[A leak in the lung: endobronchial one-way valve placement as treatment for a persistent bronchopleural fistula]. / Das Leck in der Lunge: Bronchoskopische Ventilimplantation zur Behandlung einer persistierenden bronchopleuralen Fistel.

Patients with bronchopleural fistula are at an increased risk of morbidity and mortality. Treatment of the air leak includes intrathoracic drainage, antibiotic therapy and closure of the fistula, which conventionally has been performed via surgical means. In patients with limited respiratory capacity, less-invasive alternatives are required. Here we report on a 62-year-old patient with underlying severe COPD, who was admitted with a lung abscess and consecutively developed a persistent bronchopleural fistula. Treatment involved antibiotic therapy and endobronchial one-way valve placement, which resulted in termination of the air leak and full recovery.

Incidence and outcome of weaning from mechanical ventilation according to new categories.

Weaning from mechanical ventilation was categorised as simple, difficult or prolonged by an international task force of the American Thoracic Society/European Respiratory Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine/Sociéte de Réanimation de Langue Française in 2007. This new classification has not been tested in clinical practice. The objective of the present study was to determine the incidence and outcome of weaning according to the new categories. We included medical and surgical patients who required mechanical ventilation in a prospective, multicentre, 6-month cohort study. From an initial cohort of 510 patients, 257 intubated patients started weaning. Of these patients, the cumulative incidences of simple, difficult, and prolonged weaning were 152 (59%), 68 (26%) and 37 (14%), respectively. Hospital mortality was increased in patients with prolonged (32%) but not difficult (9%) weaning in comparison with those with simple weaning (13%), overall p = 0.0205. In a multivariate logistic regression model, prolonged but not difficult weaning was associated with an increased risk of death. Ventilator-free days and intensive care unit (ICU)-free days were decreased in both difficult and prolonged weaning. In conclusion, the new weaning category prolonged weaning is associated with increased mortality and morbidity in the ICU. The new category difficult to wean was associated with increased morbidity, but not mortality.

Measuring FEV(6) for detecting early airway obstruction in the primary care setting. Quality and utility of the new PiKo-6 device.

BACKGROUND: The prevalence of asthma and chronic obstructive pulmonary disease (COPD) is high ( approximately 7.4-18%) in the general population, but less than half are diagnosed. Several studies have shown FEV(6) as a good surrogate marker for forced vital capacity (FVC) to detect airflow limitations. OBJECTIVES: The aim of this study was to evaluate if it is possible to simplify and improve the diagnosis of so far undiagnosed asthma or COPD in the primary care setting by measuring FEV(6) with a new simple screening device (PiKo-6). METHODS: 507 patients were recruited from three general practices from May to June 2005. Patients with any known pulmonary disease were excluded by questionnaire. FEV(1), FEV(6) and FEV(1)/FEV(6) were determined using a PiKo-6 device. Patients with an FEV(1)/FEV(6) <80% (PiKo positive) were invited to a standardized pulmonary function test to confirm or rule out airflow limitation. RESULTS: 401 (79.1%) patients showed FEV(1)/FEV(6) > or =80% (PiKo negative), and 106 (20.9%) patients were PiKo positive. Of the 106 PiKo-positive patients, 74 patients (14.7% of total) agreed to further studies and 18 patients (3.6%) of them suffered from COPD [COPD 0: 5 (1.0%); COPD I: 9 (1.8%); COPD II: 4 (0.8%), and none with COPD III or IV] and 14 patients (2.8%) suffered from bronchial hyperresponsiveness or asthma. In 42 patients (8.3%), the pulmonary function test was normal. CONCLUSIONS: Measurement of FEV(6) using a new simple screening device (PiKo-6) may improve the detection rate of undiagnosed airflow limitation in the primary care setting. However, patients should be carefully selected.

Recruitment of Mycobacterium tuberculosis specific CD4+ T cells to the site of infection for diagnosis of active tuberculosis.

UNLABELLED: Accurate and early diagnosis of active tuberculosis (TB) is problematic as current diagnostic methods show low sensitivity (acid-fast bacilli smears), are time-consuming (culture of biological samples) or show variable results [Mycobacterium tuberculosis (MTB)-specific PCR]. OBJECTIVES: In the course of infection, MTB-specific T cells clonally expand at the site of infection and may thus be used as diagnostic marker for active disease. DESIGN: In this cohort study, the frequency of MTB-specific, interferon (IFN)-gamma expressing CD4(+) T cells obtained from peripheral blood and the site of disease in 25 patients with suspected TB was assessed (n = 11, bronchoalveolar lavage; n = 7, pleural fluid; n = 1, ascites; n = 1, joint fluid; n = 5, cerebrospinal fluid). RESULTS: Amongst 15 patients who showed proven active TB infection, a striking increase of MTB-specific T cells was detected at the site of infection compared with peripheral blood (median increase: 28.5-fold, range: 7.25-531 fold; median of IFN-gamma-producing CD4(+) T cells from blood: 0.02%, range: 0-0.52%; median of IFN-gamma-producing CD4(+) T cells from the site of infection: 1.81%, range: 0.29-6.55%, P < 0.001). MAIN OUTCOME MEASURE: Recruitment of MTB-specific T cells to the site of infection yielded a sensitivity of 100% and specificity of 90%, irrespective of the compartment affected. CONCLUSIONS: The accumulation of MTB-specific T cells at the site of infection may prove as useful diagnostic marker for an accurate and rapid diagnosis of active TB.

[Diffuse interstitial lung diseases in association with connective tissue diseases]. / Diffuse interstitielle Lungenerkrankungen mit besonderer Berücksichtigung des rheumatischen Formenkreises.

This article gives a comprehensive overview of diffuse interstitial lung diseases especially those associated with connective tissue diseases. Interstitial lung diseases (ILD) represent a heterogeneous group of diseases of very different and partially unknown etiologies. Therefore, an exact classification of the ILD is difficult. ILDs are rarely seen in clinical practice and often lead to diagnostic problems. Diagnostic procedures require the patient's history, physical examination, serological-immunological and routine laboratory tests, pulmonary function testing, chest X-ray and high-resolution CT scan, bronchioloalveolar lavage (BAL) and bioptic procedures. The diagnostic approach to ILD requires an intensive multidisciplinary cooperation to offer early and effective therapeutic regimens.

Accuracy of echocardiographic right ventricular parameters in patients with different end-stage lung diseases prior to lung transplantation.

BACKGROUND: Because there are few data available on the accuracy of 2D-echocardiography to assess right ventricular (RV) size and function in patients with far-advanced lung disease, in this prospective study, we compared various echocardiographic RV parameters with RV volumes derived from magnetic resonance imaging (MRI). METHODS: In 32 patients (18 male, 17 female) presenting for lung transplantation, we measured RV end-diastolic and end-systolic area as well as derived RV fractional area change, long-axis diameter, short-axis diameter, tricuspid valve anulus diameter (using 2D apical or sub-costal 4-chamber view), and RV end-diastolic diameter (using M-mode in the parasternal short-axis view). These values were compared with RV end-diastolic and end-systolic volumes derived by MRI, serving as the gold standard. RESULTS: Right ventricular end-diastolic area was the most accurate echocardiographic parameter of RV size (correlation to MRI: r = 0.88, p < 0.001), followed by RV end-diastolic short-axis diameter (r = 0.75, p < 0.001), long axis diameter (r = 0.66, p < 0.001), and tricuspid valve anulus diameter (r = 0.63, p < 0.001). In contrast, M-mode measurement of RV end-diastolic diameter was possible in only 24/35 (68%) patients and showed a weak correlation to MRI-derived RV end-diastolic volume (r = 0.56, p = 0.004). Right ventricular fractional area change correlated well with MRI-derived RV ejection fraction (r = 0.84, p < 0.0001). In a sub-group analysis, patients with vascular lung disease showed best agreement between both methods for RV end-diastolic area and RV fractional area change compared with patients with restrictive or obstructive lung disease. CONCLUSION: This study shows that in patients with far-advanced lung diseases, RV end-diastolic area demonstrated the best correlation with MRI-derived measurement of RV end-diastolic volume, and RV fractional area change compared favorably with MRI-derived ejection fraction. Despite reduced image quality, especially in patients with obstructive lung disease, these parameters can yield clinically valuable information.

[Diagnosis of pulmonary embolism]. / Diagnose der Pulmonalembolie.

Although clinical assessment (good medical history, identifying patients at risk, recognition of common symptoms and signs, physical findings) and bed-side methods (standard laboratory tests, ECG, chest X-ray, arterial blood gas analysis, echocardiography and compression ultrasound of the lower extremities) for the diagnosis and/or exclusion of pulmonary embolism is highly insensitive and unspecific, the definition of clinical probability (pretest probability) still seems to be of outmost importance. Clinical probability guides initial medical therapy, induces further invasive and non invasive examinations (e.g. perfusion lung scan, spiral CT, gadolinium-enhanced magnetic resonance pulmonary angiography, contrast pulmonary angiography) and is still the final determinant in case of conflicting results of imaging modalities.

Aerobic endurance training program improves exercise performance in lung transplant recipients.

STUDY OBJECTIVE: To determine whether an aerobic endurance training program (AET) in comparison to normal daily activities improves exercise capacity in lung transplant recipients. PATIENTS AND STUDY DESIGN: Nine lung transplant recipients (12+/-6 months after transplant) were examined. All patients underwent incremental bicycle ergometry with the work rate increased in increments of 20 W every 3 min. Identical exercise tests were performed after 11+/-5 weeks of normal daily activities and then after a 6-week AET. The weekly aerobic training time increased from 60 min at the beginning to 120 min during the last week. Training intensity ranged from 30 to 60% of the maximum heart rate reserve. RESULTS: Normal daily activities had no effect on exercise performance. The AET induced a significant decrease in resting minute ventilation from 14+/-5 to 11+/-3 L/min. At an identical, submaximal level of exercise, a significant decrease in minute ventilation from 47+/-14 L/min to 39+/-13 L/min and heart rate from 144+/-12 to 133+/-17 beats/min, before and after the AET, was noted. The increase in peak oxygen uptake after AET was statistically significant (1.13+/-0.32 to 1.26+/-0.27 L/min). CONCLUSIONS: These data demonstrate that normal daily activities do not affect exercise performance in lung transplant recipients > or = 6 months after lung transplantation. An AET improves submaximal and peak exercise performance significantly.

The effect of lung transplantation on the neural drive to the diaphragm in patients with severe COPD.

Little is known about the effects of lung transplantation (LT) on the neural drive to the diaphragm and on the endurance of respiratory muscles in patients with severe chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate these effects of single-lung (SLT) and double-lung transplantation (DLT). The neural drive to the diaphragm was assessed during fatiguing inspiratory threshold loading manoeuvres in six SLT recipients, six DLT recipients and seven patients with severe COPD, by using diaphragmatic surface electromyograms. During threshold loading, the patients had to generate 80% of their maximal transdiaphragmatic pressure with each breath. The endurance of inspiratory muscles was defined as the time from the beginning of a resistive breathing trial until exhaustion (t lim). In DLT recipients and even in SLT recipients (on both sides), neural activation of the diaphragm was significantly lower than in COPD patients (p < 0.05). However, no statistically significant difference in t lim was seen between LT recipients and COPD patients. The data suggest that single-lung and double-lung transplantations cause a significant decrease of the neural drive to the diaphragm, while the endurance of inspiratory muscles is well-preserved in patients with advanced chronic obstructive pulmonary disease. This may contribute to reduced sensation of inspiratory effort during ventilatory stress, thus improving the quality of life.

Severe pulmonary hypertension reversed by antibiotics in a patient with Whipple's disease.

The case is described of a 58 year old man with systemic Whipple's disease with pericardial and pleural effusions and severe pulmonary hypertension. After three months of antibiotic treatment there was a complete resolution, not only of the symptoms known to be associated with Whipple's disease (diarrhoea, arthralgia, pericardial and pleural effusions), but also of pulmonary hypertension.

Doppler assessment of pulmonary haemodynamics in chronic hypoxic lung disease.

Various methods of Doppler echocardiography are useful in the analysis of flow dynamics within the heart and the pulmonary circulation in patients with COPD. In addition, to distinguish patients with increased pulmonary artery pressures from those with normal pressures, Doppler techniques provide quantitative methods for estimating pulmonary artery pressures non-invasively. Doppler echocardiography can be performed repeatedly and can thus be used to assess serial changes in the clinical state of a patient or in the response to certain pharmaceutical interventions in the pulmonary vascular bed. The most useful and accurate method of estimating pulmonary artery pressures in patients with chronic hypoxic lung disease is the systolic trans-tricuspid gradient, calculated from tricuspid regurgitation detected by continuous wave Doppler echocardiography with estimation of the right ventricular pressure, followed by the acceleration time from pulmonary flow analysis using pulsed Doppler techniques. New contrast materials to enhance the continuous wave Doppler signal and transoesophageal echocardiography may provide even more satisfactory results in the future.

[Chronic thromboembolic pulmonary hypertension and its treatment with pulmonary thrombendarterectomy]. / Die chronisch-thromboembolische pulmonale Hypertension und ihre Behandlung mit der pulmonalen Thrombendarteriektomie.

Chronic recurrent pulmonary embolism can lead to extensive pulmonary hypertension by obstruction of the pulmonary vessels. Pulmonary thrombendarteriectomy is a new approach to normalizing the elevated pulmonary vascular resistance by removal of the adsorbed thrombi. Between 1992 and 1994 we have operated on 8 patients aged between 34 and 62 years. The first patient died due to extensive reperfusion edema, all others showed significant improvement in hemodynamic parameters (mean pulmonary artery pressure preop. 63 +/- 5 mmHg; postop. 30 +/- 9 mmHg; Cardiac Index preop. 2.0 +/- 0.2 l/min; postop. 3.5 +/- 0.5 l/min; pulmonary vascular resistance preop. 1169 +/- 75 dyn; postop. 228 +/- 55 dyn) and exercise performance (NYHA classification preop. III-IV, postop. I-II). Pulmonary thrombendarteriectomy represents an efficient method to normalize elevated pulmonary pressure and exercise performance of patients with far-advanced chronic thromboembolic pulmonary hypertension.

Effect of lung transplantation on diaphragmatic function in patients with chronic obstructive pulmonary disease.

BACKGROUND: To date there are no data on the effects of lung transplantation on diaphragmatic function in patients with end stage chronic obstructive pulmonary disease (COPD). It is not known whether the relation between the transdiaphragmatic pressure (PDI) and lung volume is altered in recipients after transplantation as a result of changes in diaphragmatic structure caused by chronic hyperinflation. The effect of lung transplantation on diaphragmatic strength was determined in patients with COPD and the relation between postoperative PDI and lung volume analysed. METHODS: Diaphragmatic strength was assessed in eight double lung transplant recipients, six single lung transplant recipients, and in 14 patients with COPD whose lung function was similar to those of the transplant recipients preoperatively. PDI obtained during unilateral and bilateral phrenic nerve stimulation at 1 Hz (twitch PDI) at functional residual capacity (FRC) and during maximal sniff manoeuvres (sniff PDI) at various levels of inspiratory vital capacity (VCin) served as parameters for diaphragmatic strength. Sniff PDI assessed at the various VCin levels were used to analyse the PDI/lung volume relation. RESULTS: Lung transplantation caused a reduction in lung volume, especially in the double lung transplant recipients. As a consequence sniff PDI was higher in the double lung transplant recipients than in the patients with COPD at all levels of VCin analysed. However, sniff PDI values analysed at comparable intrathoracic gas volumes were not reduced in the patients with COPD when compared with those who underwent lung transplantation. Bilateral twitch PDI values were similar in the patients with COPD and in the lung transplant recipients. In the single lung transplant recipients unilateral twitch PDI values were similar on the transplanted and the non-transplanted side. The relation between PDI and lung volume was similar in the patients with COPD and in the lung transplant recipients. CONCLUSIONS: In patients with COPD lung transplantation leads to an increase the maximal sniff induced PDI values by placing the diaphragm in a more favourable position for pressure generation. Since patients with COPD and postoperative lung transplant recipients showed similar PDI/lung volume relations, this suggests that chronic pulmonary hyperinflation does not cause major functional alterations of the diaphragm.

Effect of lung transplantation on right and left ventricular volumes and function measured by magnetic resonance imaging.

To evaluate the effect of lung transplantation on right ventricular (RV) and left ventricular (LV) volumes and function, magnetic resonance imaging (MRI) was performed in 11 patients before and 6 to 24 months after single (n = 7) or double (n = 4) lung transplantation as well as in 15 healthy control subjects. Prior to transplantation, RV end-diastolic (RVEDVI, ml/m2) and end-systolic (RVESVI, ml/m2) volume indices were significantly increased in patients compared with those in control subjects. RV ejection fraction (RVEF, %), although within the lower normal range, was significantly reduced. In contrast, LV volume indices (ml/m2) were significantly smaller in patients than in control subjects, whereas LV ejection fraction (LVEF, %) was not different from that in normal subjects. After lung transplantation, MRI revealed a significant reduction in RVEDVI from 73 +/- 29 to 54 +/- 14 (p = 0.03) and RVESVI from 38 +/- 23 to 20 +/- 6 (p = 0.01) with a concomitant significant increase in RVEF from 48 +/- 14 to 63 +/- 6 (p = 0.01). Consecutively, the LV expanded to normal (LVEDVI from 49 +/- 12 to 65 +/- 14, p = 0.01; LVESVI from 23 +/- 9 to 28 +/- 7, p = 0.05), whereas LVEF remained unchanged (55 +/- 9 versus 56 +/- 8).

Early experience with sequential bilateral lung transplantation.

We performed 20 sequential bilateral lung transplantation in 19 consecutive patients from April 1990 to May 1992. Perioperative mortality was low (2 patients). One-year actuarial survival was 70%. All survivors had normal blood oxygen tension (82 mm Hg, mean) while breathing room air and continuing improvement of pulmonary function. Bronchial dehiscence did not occur. Stents were implanted in 7 patients to control bronchial stenosis. Aggressive treatment of graft rejection has been effective in preventing obliterative bronchiolitis.

[High-resolution computed tomography (HR-CT) of the lung following lung transplantation]. / Hochauflösende Computertomographie (HR-CT) der Lunge nach Lungentransplantation.

We report our high-resolution computed tomography (HRCT) and conventional CT findings after lung transplantation in 20 patients. Sixty-four examinations were performed 7-511 days after transplantation. The radiological observations were then correlated with the clinical results. The pathological findings in the early postoperative phase were pleural effusion, edema, and pulmonary consolidation. The HRCT findings associated with acute rejection were nonspecific. Dilation and thickening of the walls of the peripheral bronchi is a common, but non-specific feature in bronchiolitis obliterans. The manifestations of posttransplant lymphoproliferative disorder are discussed in two patients.

Pulsed Doppler echocardiography to assess pulmonary artery hypertension in chronic obstructive pulmonary disease.

Noninvasive assessment of pulmonary artery hypertension would be of great value in patients with chronic obstructive pulmonary disease (COPD). Although continuous wave Doppler echocardiographic measurement of right atrial to right ventricular pressure gradient is the most useful method of noninvasive assessment of pulmonary artery hypertension, this technique is often limited in patients with COPD. In order to evaluate the usefulness of pulsed Doppler echocardiography, for the estimation of pulmonary artery pressure in COPD patients in whom continuous wave Doppler ultrasound has failed, we compared right ventricular systolic time intervals: pre-ejection period (PEP, ms), acceleration time (AT, ms), right ventricular ejection time (RVET, ms), and AT/RVET and PEP/RVET ratios, as measured by pulmonary artery pulsed Doppler traces, in 30 COPD patients, with the time intervals of 15 age- and sex-matched healthy volunteers, using the subcostal approach. In addition, right ventricular systolic time intervals of the COPD patients were correlated with invasive catheterization data (systolic and mean pulmonary artery pressure (PAPs and PAPm). AT and AT/RVET were significantly shorter in COPD patients (AT 92 +/- 4.3 ms; AT/RVET 0.38 +/- 0.03) as compared with healthy volunteers (AT 132 +/- 4.5 ms; p < 0.001; AT/RVET 0.46 +/- 0.02; p < 0.005), whereas RVET, PEP and PEP/RVET were not significantly different in both groups. A significant correlation was demonstrated between AT and PAPs (r = -0.76; p < 0.001) and PAPm (r = -0.82; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)