Idiopathic pleuroparenchymal fibroelastosis (PPFE) - A case study of a rare entity.

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) was recognized as a rare new entity. We report the case of a 63 years old female suffering from progressive dyspnea and dry cough for three years. Two years before admission to our hospital, idiopathic pulmonary fibrosis (IPF) was diagnosed in another hospital and treatment with prednisolone and N-acetylcysteine (NAC) was commenced. At admission HRCT showed upper lobe dominant fibrosis and associated pleural thickening. Surgical biopsies were re-evaluated and revealed fibroelastosis with pleural thickening and a probable UIP pattern, consistent with idiopathic PPFE. Treatment with pirfenidone was initiated due to progression under prednisolone and NAC. Upper lobe predominant pleural thickening with associated subpleural fibrotic changes should raise suspicion of PPFE.

[Epidemiology and Clinical Presentation of Sarcoidosis]. / Epidemiologie und klinisches Erscheinungsbild der Sarkoidose.

Sarcoidosis is a systemic disease of unknown aetiology. Typical histology shows epithelioid cell granulomas, and typical immunopathology enhanced Th1 type immune responses in the involved organs. The disease occurs worldwide, but more frequently in northern countries than in the south. In Germany, the incidence is estimated to be 10 per 100,000, and the prevalence 44-48 per 100,000. Sarcoidosis usually affects adults under 50 years of age, but can also be seen in children, adolescents and in the elderly. Women are more frequently affected than men. Familial clusters can occur. The clinical presentation of sarcoidosis varies widely and depends on the manifestations in the individual organ. Systemic symptoms include fatigue, night sweats, weight loss, fever, arthralgia and myalgia. Organ-specific symptoms include cough and dyspnoea, with pulmonary involvement, headache and palsy in neurosarcoidosis, arrhythmias and heart failure in cardiac sarcoidosis, and manifold skin lesions with skin involvement. Relapses are rarely seen in acute sarcoidosis, whereas the chronic form tends to relapse more frequently. Löfgren's syndrome, a specific phenotype of acute sarcoidosis, is characterised by bihilar lymphadenopathy, ankle arthritis and erythema nodosum. Chronic sarcoidosis can be asymptomatic, despite radiological changes, which may be extensive. By definition, sarcoidosis has become chronic after 2 years of disease with ongoing signs of activity. The long-term prognosis is generally good, but depends on the different organ manifestations and complications.

[Clinical experience with pirfenidone for the treatment of idiopathic pulmonary fibrosis]. / Klinische Erfahrungen mit Pirfenidon in der Therapie der idiopathischen Lungenfibrose.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with an estimated median survival of only 3 years after diagnosis. Pirfenidone is the only medication approved in the European Union for the treatment of adults with mild to moderate lung fibrosis. We analyzed data on safety and efficacy of pirfenidone in the treatment of patients with IPF in our centre. PATIENTS AND METHODS: From 2006 to 2012, 45 patients (28 inside clinical trials, 17 outside) with mild to moderate IPF were treated with pirfenidone. Clinical data, results of lung function tests, and radiological findings as well as data about side effects were collected routinely. RESULTS: The mean duration of treatment per patient was 48 [range 3-321] weeks. 16 patients (35 %) received pirfenidone as monotherapy and 29 (65 %) in combination with corticosteroids and/or N-acetylcysteine (NAC). At the end of the follow-up period 28 of 40 patients (70 %) with treatment duration > 3 months were in a stable condition. 26 patients (58 %) suffered from side effects, mostly gastrointestinal (17 [38 %]). Pirfenidone was discontinued by six patients (13 %) because of side effects. The median survival after the start of pirfenidone was 3.8 years. CONCLUSION: Pirfenidone alone or in combination with NAC and/or corticosteroids was generally well tolerated. Severe side effects were rare. The course of the disease was stable during treatment with pirfenidone in two out of three patients. Our results are in line with the previous published safety and efficacy data on pirfenidone as treatment for IPF.

Influence of disease control with pegvisomant on sleep apnoea and tongue volume in patients with active acromegaly.

OBJECTIVES: Sleep apnoea has been consistently reported to occur in acromegaly. In uncontrolled patients, the severity of sleep apnoea influences physical activity in the daytime. We investigated the influence of disease activity on tongue volume and sleep apnoea treated with the GH receptor antagonist pegvisomant in poorly controlled patients with acromegaly under octreotide. DESIGN AND METHODS: A total of 12 patients with active acromegaly (six females; six males; mean age 57+/-15 years; body mass index 29.4+/-4.2 kg/m(2); mean+/-S.D.) were treated with pegvisomant (13.5+/-5.0 mg/die) for 6 months. Tongue volume was examined by magnetic resonance imaging, and sleep apnoea was characterized by polysomnography before and after 6 months of treatment with pegvisomant. The mandibular length was determined by lateral X-ray films. RESULTS: IGF1 levels decreased after 6 months in all patients (407+/-114 to 199+/-23 microg/l; P=0.0001). The tongue volume decreased (105+/-33 to 83+/-33 ml; P=0.007) as well as the apnoea-hypnoea index (23+/-22 to 18+/-18/h; P=0.0066). The mandibular length correlated with the initial tongue volume (r(2)=0.6072, P=0.0028). CONCLUSION: In conclusion, successful treatment with pegvisomant can decrease tongue volume, which has benefits for coexisting sleep disordered breathing.

Long-term outcome of Guillain-Barré syndrome.

OBJECTIVES: To investigate long-term neurological residua after Guillain-Barré syndrome (GBS) and to evaluate the predictive value of respiratory insufficiency during the acute stage of the disease. METHODS: Thirty-four patients with GBS including 5 patients with Miller-Fisher syndrome admitted to a university hospital between 1994 and 2002 underwent a neurological and electrophysiological follow-up examination 7 - 86 months after onset of GBS. RESULTS: Of the 34 patients, 5 patients had completely recovered, 11 patients demonstrated mild residual symptoms and/or signs, and 18 patients presented with functionally relevant neurological deficits predominantly in the lower extremity, although all patients could walk without assistance and none showed respiratory failure. Nerve conduction studies revealed abnormal findings in 30 patients. Autonomic function testing of the cardiovascular system showed a pathological blood pressure response to standing in 27 of 33 patients. No association was found between the course of the disease and sleep-disordered breathing at follow-up. Age at onset, need for mechanical ventilation, and duration of the plateau phase correlated with severity of neurological residua at follow-up. CONCLUSIONS: There was a high persistence of residual sensorimotor signs and symptoms after GBS in our cohort. In addition, abnormal blood pressure declines not associated with clinically overt orthostatic dysregulation were detected in the majority of our patients at follow-up. This is in contrast to previous reports describing a gradual improvement of autonomic dysfunction after 2 - 18 months. A combined prognostic score based on patient age, duration of the plateau phase, and ventilatory failure in the acute stage of GBS might predict the long-term outcome.

Effects of octreotide on sleep apnoea and tongue volume (magnetic resonance imaging) in patients with acromegaly.

OBJECTIVES: Sleep apnoea has been consistently reported to occur in acromegaly. Both obstructive apnoeas, in which apnoeas are due to intermittent obstruction of the upper airways, as well as central apnoeas are known to occur. Because the relationship between disease activity and severity of sleep apnoea is currently unclear, we have performed a prospective study to address this issue. DESIGN AND METHODS: In 14 newly diagnosed patients with active acromegaly (eight females and six males; mean age 57+/-4 years; IGF-I 583+/-48 microg/l; GH 13.5+/-7.0 microg/l (means+/-s.e.m.)), tongue volume and signal intensity of the tongue were examined by magnetic resonance imaging and sleep apnoea was characterised by polysomnography before and after 6 months of treatment with octreotide acetate (Sandostatin LAR 10-30 mg every 4 weeks i.m.). RESULTS: The initial tongue volume was significantly higher in patients with acromegaly (151+/-9 ml; females 133+/-10 ml; males 172+/-10 ml) in comparison with the body mass index (BMI)- and age-matched healthy control group (97+/-5 ml, P<0.001; females 75+/-1 ml, P<0.001; males 120+/-3 ml, P<0.003). After treatment with octreotide, IGF-I was normalised within the age-adjusted normal range in 50% of the patients. In these patients, tongue volume significantly decreased (120+/-14 ml, P<0.05) in comparison with the persistent uncontrolled group of acromegalics (137+/-10 ml, P=not significant). Overall, tongue volume (128+/-8 ml, P<0.05) and the signal intensity ratio of the tongue decreased significantly after treatment with octreotide acetate (120+/-3 vs 105+/-3, P=0.003). The BMI-adjusted tongue volume correlated with IGF-I levels (r=0.60, P<0.002) and the disease duration (r=0.71, P=0.006). At baseline, 50% had obstructive sleep apnoea with a mean respiratory disturbance index (RDI) of >20/h (range 5.1-91.5) and no patient had central sleep apnoea. After 6 months of octreotide treatment, there was a 28+/-10% decrease in RDI. However, RDI did not correlate with IGF-I or GH levels, but correlated positively with BMI (r=0.58, P=0.001) and age (r=0.46, P=0.02). CONCLUSIONS: Obstructive sleep apnoea but not central sleep apnoea frequently occurs in patients with active acromegaly. Successful treatment with octreotide can decrease tongue volume, which may have benefits for coexisting sleep-disordered breathing.

[Adaptive servoventilation: effect on Cheyne-Stokes-Respiration and on quality of life]. / Adaptive Servoventilation bei chronischer Herzinsuffizienz: Wirkung auf Cheyne-Stokes-Atmung und Lebensqualität.

BACKGROUND: Adaptive servo-ventilation (ASV) (AutoSetCS, ResMed) is a novel non-invasive ventilation modality for the treatment of Cheyne-Stokes-Respiration (CSR) in patients with heart failure. This study aimed to investigate the effect of ASV on sleep disordered breathing (SDB), afternoon nap duration, urine voidings, and quality of life. METHODS: 11 patients with CSR due to heart failure (EF < 40 %) were treated with ASV for a period of 6 weeks. Apnea-Hypopnoe-Index (AHI), Arousalindex (AI), duration of afternoon nap, number of voidings, and heart specific quality of life were assessed before and at the end of the treatment period. RESULTS: The average usage time of ASV was 5.8 +/- 2.1/h per day. With ASV the AHI was reduced from 48.2 +/- 11.6 to 6.4 +/- 8.3/h (p < 0.001) and the AI from 33.9 +/- 12.5 to 18.4 +/- 9.3 /h (p < 0.05). The afternoon nap duration was significantly less (1.4 +/- 0.6 vs. 0.7 +/- 0.4 hours per day; p = 0.004) as was the number of nocturnal voidings (2.9 +/- 0.7 vs. 1.1 +/- 0.3 per night; p = 0.007). There was a significant improvement in heart specific quality of life as measured with the Minnesota Living with heart failure questionnaire (43.5 +/- 21.1 vs. 27.6 +/- 15.7 (p = 0.02). CONCLUSION: ASV is well tolerated and improves SDB and quality of life of patients with heart failure with CSR.

[Validation of microMESAM as screening device for sleep disordered breathing]. / Validierung von microMESAM als Screeningsystem für schlafbezogene Atmungsstörungen.

INTRODUCTION: Polysomnography (PSG) is considered the gold standard in the diagnosis of sleep disordered breathing (SDB). Because of costs and labor-intensity it is, however, performed last in graded diagnostic protocols that often involve respiratory pressure measurements via nasal canula as an alternative sensitive method for SDB detection. MicroMESAM, a newly developed screening device based on this method, allows automated analysis of apnoeas, hypopnoeas and snoring. AIM AND METHODS: To validate the device, we first compared signal quality of MicroMESAM flow-time curves with those generated by a pneumotachograph. Then, in 50 patients suspected of having obstructive sleep apnoea, we compared MicroMESAM-generated automated analysis with manually scored results of simultaneously collected PSG data. RESULTS: MicroMESAM-generated flow-time curves correspond with pneumotachograph-generated curves in 95% of respiratory events, resulting in less 4 +/- 2% difference in respective area under the curves. MicroMESAM and PSG generated numbers of apnoeas (r = 0.99) and hypopnoea (r = 0.81), as well as AHI (r = 0.98) correlated highly, displaying mean differences in AHI of 3.8, and in 1.96 sigma interval of + 11.1 to - 3.5/h. Sensitivities and specificities for SDB were 97.3%, respective 46% at SDB-defining AHI of 5, and 100%, respective 87.5%, at SDB-defining AHI of 10. SUMMARY: MicroMESAM-generated flow-time curves correspond well with pneumotachograph generated curves, producing automated AHIs that are highly sensitive in detecting SDB. MicroMESAM, therefore, is suitable as a screening device for SDB.

[Pulse oximetry screening for sleep-disordered breathing in stroke]. / Pulsoximetrie als Schlafapnoescreening bei Schlaganfallpatienten.

BACKGROUND: The prevalence of sleep-disordered breathing, particularly obstructive sleep apnea, among stroke patients is high. Routine screening with the current diagnostic gold standard of polysomnography is not feasible. Pulse oximetry could be a simple screening test. METHODS: The signal of pulse oximetry, recorded during full polysomnography in 184 stroke patients during neurological rehabilitation, was analyzed automatically by software for desaturations >/= 4 %. The polysomnographic apnoea-hypopnoea-index (AHI) was used as the diagnostic gold standard and compared with the oxygen desaturation index (ODI). RESULTS: Correlation between AHI of PSG and ODI of oximetry was r = 0.84 (p < 0.001). Dependent on the definition of SDB (AHI 10, 15, 20 or 30/h) and the cut-off-point for the ODI (e. g. 15/h) sensitivity was 32 - 83 % and specificity 99 - 96 %. The diagnostic accuracy as determined by the area under the ROC-curve was 96 %. CONCLUSION: Automated analysis of pulse oximetry gives reasonable results for screening for SDB in stroke patients and could be used in populations with high pre-test probability.

Treatment of obstructive sleep apnoea with nasal continuous positive airway pressure in stroke.

The prevalence of obstructive sleep apnoea (OSA) following stroke is high and OSA is associated with increased morbidity, mortality and poor functional outcome. Nasal continuous positive airway pressure (nCPAP) is the treatment of choice for OSA, but its effects in stroke patients are unknown. The effectiveness and acceptance of treatment with nCPAP in 105 stroke patients with OSA, admitted to rehabilitation was prospectively investigated. Subjective wellbeing was measured with a visual analogue scale in 41 patients and 24-h blood pressure was determined in 16 patients before and after 10 days of treatment. Differences were compared between patients who did and did not accept treatment. There was an 80% reduction of respiratory events with concomitant increase in oxygen saturation and improvement in sleep architecture. No serious side-effects were noticed. Seventy-four patients (70.5%) continued treatment at home. Nonacceptance was associated with a lower functional status, as measured by the Barthel Index, and the presence of aphasia. Ten days after initiation of nCPAP, compliant users showed a clear improvement in wellbeing (differences in visual analogue scale (deltaVAS) mean+/-SD 26+/-26 mm) versus noncompliant patients (deltaVAS 2+/-25 mm, p=0.021). Only the compliant group had a reduction in mean nocturnal blood pressure (deltaBP; -8+/-7.3 mmHg versus 0.8+/-8.4 mmHg, p=0.037). Stroke patients with obstructive sleep apnoea can be treated effectively with nasal continuous positive airway pressure and show a similar improvement and primary acceptance to obstructive sleep apnoea patients without stroke. Continuous positive airway pressure acceptance is associated with improved wellbeing and decreased nocturnal blood pressure.

Sleep and stroke.

Although the incidence of strokes is not maximal during sleeping hours, several lines of evidence make it probable that sleep in combination with breathing disorders like snoring and obstructive apneas are risk factors for ischemic strokes: the natural history of snoring and obstructive sleep apnea shows a higher incidence of strokes than in undisturbed sleep, the prevalence of snoring and sleep apneas in stroke patients is by far higher than in non-stroke patients; odds-ratios of stroke are higher in snorers and apneic patients than in normals, although the correction for confounders seems never perfect. The analysis of potential pathomechanisms linking sleep disordered breathing to strokes is another approach to the main topic: snoring and sleep apnea induce hypertension and arrhythmia, the carotid intima-media-thickness is increased, carotid atheromas are more common among apneics than among normals, the flow in the A. cerebri media is as well altered as the reaction to angiotensine II, noradrensine, isoproterenol and bradykinin. Homocysteine is increased, plasminogen activator inhibitor type 1 is inhibited and platelets are activated leading to an increased risk of thrombosis. There are no studies showing the effectiveness of treatment with nasal continuous positive airway pressure (nCPAP) on the rehabilitation of apneic stroke patients, but the outcome of non-apneic stroke patients is better than that of apneic stroke patients.

Fibrinogen levels and obstructive sleep apnea in ischemic stroke.

The plasma level of fibrinogen is felt to be an independent risk factor for vascular events. Obstructive sleep apnea (OSA) has a high prevalence in patients with stroke and may also be an independent risk factor. The aim of our study was to determine the association between OSA and plasma levels of fibrinogen in patients with stroke. Polysomnography was performed during neurological rehabilitation in 113 patients (82 men, 31 women, age 58 +/- 11.1 yr, mean +/- SD) with ischemic stroke. OSA was absent (RDI < 5) in 44 patients, 42 had mild OSA (5 < or = RDI < 20), and 27 had moderate to severe OSA (RDI > or = 20). Parameters of OSA (respiratory disturbance index [RDI], oxygen indices) were correlated to plasma levels of fibrinogen, measured in the morning after admission to rehabilitation. Fibrinogen was positively correlated with RDI (r = 0.24, p = 0.007), duration of the longest apnea (r = 0.18, p = 0.049), and negatively correlated with several oxygen indices including average minimal oxygen saturation (r = -0.41, p < 0.001). Correlation coefficients were slightly higher when excluding patients with stroke of presumed cardiac origin. Multiple linear regression identified minimal mean oxygen saturation and sex as independent predictors of fibrinogen level. The correlation between severity of coexisting OSA and fibrinogen level in patients with stroke suggests a possible pathophysiological mechanism for an increased risk of stroke in patients with OSA.

Two months auto-adjusting versus conventional nCPAP for obstructive sleep apnoea syndrome.

Autoadjusting nasal continuous positive airway pressure (CPAP) greatly reduces the apnoea/hypopnoea index (AHI), and affords a significant reduction in median pressure (P50) compared-with manually titrated conventional nasal CPAP. The aim of the present study was to test whether these benefits were maintained in the medium term at home, in a double-blind crossover study. Ten sequential subjects (mean AHI 52.9 x h(-1)) were enrolled. After a manual titration, subjects were randomly allocated to 2 months autoadjusting nasal CPAP (AutoSet), followed by 2 months with the AutoSet device in fixed pressure mode at the manually titrated pressure, or vice versa. The machine-scored AHI, P50, and median leak were recorded on 12 nights in each arm, and averaged. Mean+/-SEM AHI was 4.0+/-0.3 x h(-1) in auto mode, and 3.7+/-0.3 x h(-1) in manual mode (NS). Mean+/-SEM P50 was 7.2+/-0.4 cmH2O auto, 9.4+/-0.6 cmH2O manual, average reduction 23+/-4% (p<0.0001). Auto "recommended" pressure was (mean+/-SEM) 10.1+/-0.5 cmH2O (p=0.04 with respect to manual) and peak pressure typically 1 cmH2O higher. Median (+/-SEM) leak was 0.181+/-0.006 L x s(-1) auto (and uncorrelated with AHI or pressure), 0.20+/-0.006 L x s(-1) manual (p=0.003). Compliance was 6.3+/-0.4 h in auto mode and 6.1+/-0.5 h in fixed mode (NS). Apnoea/hypopnoea index during 2 months of home autoadjusting nasal continuous positive airway pressure is comparable to that during conventionally titrated fixed pressure continuous positive airway pressure, while affording a 23% reduction in median pressure but no increase in compliance. Leak did not importantly affect autoadjustment.

Sleep-disordered breathing among patients with first-ever stroke.

Sleep-disordered breathing (SDB) in the form of obstructive sleep apnea is a possible risk factor for stroke. We carried out a cross-sectional survey out in a rehabilitation center among patients with first-ever stroke to further determine the incidence and types of SDB and its relationship to known risk factors for stroke. Full polysomnography was performed in 147 consecutive patients (95 men, 52 women, age 61+/-10 years) admitted to our neurological Rehabilitation Department 46+/-20 days after first-ever stroke. Subjective sleepiness (Epworth Sleepiness Scale), vascular risk factors, anthropometric data, and polysomnographic findings were compared between stroke patients with varying degrees of SDB. With a cutoff point for the respiratory disturbance index (RDI) of 5, 10, 15, or 20 the respective prevalence of SDB was 61%, 44%, 32%, and 22%. The type of SDB was generally obstructive, with dominant central apneas in only 6% of patients. Patients with an RDI of 20 or higher had less REM sleep, thicker necks, and a more central type of obesity. Even in patients with an RDI of 20 or higher subjective sleepiness, although higher than in those without SDB, was not a predominant symptom. Snoring and anthropometric data suggest that obstructive SDB may have existed prior to stroke. The prevalence of hypertension and coronary heart disease were higher among stroke patients with an RDI of 20 or higher than in those without SDB. We conclude that the prevalence of SDB among patients with stroke is high. Examination of stroke should include screening for SDB.

[Obstructive sleep apnea syndrome. A probably cause of therapy refractory hypertension in intracerebral hemorrhage]. / Obstruktives Schlafapnoesyndrom. Wahrscheinliche Ursache einer therapieresistenten Hypertonie bei intrazerebraler Blutung.

There is clear evidence for obstructive sleep apnea as an independent cause of arterial hypertension. We report a case of intracranial hemorrhage with systemic hypertension resistant to antihypertensive medication, which could only be adjusted after effective treatment of coexisting sleep-disordered breathing. The 36 year old male (body mass index 31 kg/m2) was admitted to hospital three weeks before for intracranial bleeding at the left external capsule. Diagnosis of primary hypertension was made after extensive work-up in the acute hospital. Blood pressure was adjusted with five-fold antihypertensive medication at the time of admission to neurological rehabilitation, but was still elevated with "non-dipping" as determined by long-term measurement despite medications above the recommended dosages. Polysomnography confirmed the diagnosis of obstructive sleep apnea. 10 days after initiation of treatment with nasal CPAP blood pressure control was easier with normal dipping at night. Medication could be reduced during rehabilitation with further reduction after discharge. Moderate obstructive sleep apnea appears to be the cause of severe hypertension resistant to pharmacological therapy in this patient. The case underlines the impact of diagnosis and treatment of sleep-disordered breathing for the secondary prevention of stroke.