Ahmet Baydur

Long term non-invasive ventilation in the community for patients with musculoskeletal disorders: 46 year experience and review

BACKGROUND A study was undertaken to assess the long term physiological and clinical outcome in 79 patients with musculoskeletal disorders (73 neuromuscular, six of the chest wall) who received non-invasive ventilation for chronic respiratory failure over a period of 46 years. METHODS Vital capacity (VC) and carbon dioxide tension (Pco 2) before and after initiation of ventilation, type and duration of ventilatory assistance, the need for tracheostomy, and mortality were retrospectively studied in 48 patients who were managed with mouth/nasal intermittent positive pressure ventilation (M/NIPPV) and 31 who received body ventilation. The two largest groups analysed were 45 patients with poliomyelitis and 15 with Duchennes muscular dystrophy. Twenty five patients with poliomyelitis received body ventilation (for a mean of 290 months) and 20 were supported by M/NIPPV (mean 38 months). All 15 patients with Duchennes muscular dystrophy were ventilated by NIPPV (mean 22 months). RESULTS Fourteen patients with poliomyelitis on body ventilation (56%) but only one on M/NIPPV, and 10 of 15 patients (67%) with Duchennes muscular dystrophy eventually received tracheostomies for ventilatory support. Five patients with other neuromuscular disorders required tracheostomies. Twenty of 29 tracheostomies (69%) were provided because of progressive disease and hypercarbia which could not be controlled by non-invasive ventilation; the remaining nine were placed because of bulbar dysfunction and aspiration related complications. Nine of 10 deaths occurred in patients on body ventilation (six with poliomyelitis), although the causes of death were varied and not necessarily related to respiratory complications. A proportionately greater number of patients on M/NIPPV (67%) reported positive outcomes (improved sense of wellbeing and independence) than did those on body ventilation (29%, p<0.01). However, other than tracheostomies and deaths, negative outcomes in the form of machine/interface discomfort and self-discontinuation of ventilation also occurred at a rate 2.3 times higher than in the group who received body ventilation. None of the six patients with chest wall disorders (all on M/NIPPV) required tracheostomy or died. Hospital admission rates increased nearly eightfold in patients receiving body ventilation (all poliomyelitis patients) compared with before ventilation (p<0.01) while in those supported by M/NIPPV they were reduced by 36%. CONCLUSIONS Non-invasive ventilation (NIV) in the community over prolonged periods is a feasible although variably tolerated form of management in patients with neuromuscular disorders. While patients who received body ventilation were followed the longest (mean 24 years), the need for tracheostomy and deaths occurred more often in this group (most commonly in the poliomyelitis patients). Despite a number of discomforts associated with M/NIPPV, a larger proportion of patients experienced improved wellbeing, independence, and ability to perform daily activities.

A Nonlinear Model of Cardiac Autonomic Control in Obstructive Sleep Apnea Syndrome

Using the Volterra–Wiener approach, we employed a minimal model to quantitatively characterize the linear and nonlinear effects of respiration (RCC) and arterial blood pressure (ABR) on heart rate variability (HRV) in normal controls and subjects with moderate-to-severe obstructive sleep apnea syndrome (OSAS). Respiration, R–R interval (RRI), blood pressure (BP) and other polysomnographic variables were recorded in eight normal controls and nine OSAS subjects in wakefulness, Stage 2 and rapid eye-movement sleep. To increase respiratory and cardiovascular variability, a preprogrammed ventilator delivered randomly timed inspiratory pressures that were superimposed on a baseline continuous positive airway pressure. Except for lower resting RRI in OSAS subjects, summary statistical measures of RRI and BP and their variabilities were similar in controls and OSAS. In contrast, RCC and ABR gains were significantly lower in OSAS. Nonlinear ABR gain and the interaction between respiration and blood pressure in modulating RRI were substantially reduced in OSAS. ABR gain increased during sleep in controls but remained unchanged in OSAS. These findings suggest that normotensive OSAS subjects have impaired daytime parasympathetic and sympathetic function. Nonlinear minimal modeling of HRV provides a useful, insightful, and comprehensive approach for the detection and assessment of abnormal autonomic function in OSAS.

Fatigue and plasma cytokine concentrations at rest and during exercise in patients with sarcoidosis

Background:  Patients with sarcoidosis exhibit exercise intolerance‐related fatigue and increased levels of circulating proinflammatory cytokines at rest. Exercise may result in increased plasma cytokine levels (PCLs) in healthy adults, but such a relationship has not been studied in sarcoidosis patients.

Autonomic Cardiovascular Control Following Transient Arousal From Sleep: A Time-Varying Closed-Loop Model

Recent studies suggest that exposure to repetitive episodes of hypoxia and transient arousal can lead to increased risk for cardiovascular disease in patients with obstructive sleep apnea syndrome (OSAS). To obtain an improved understanding of and to quantitatively characterize the autonomic effects of arousal from sleep, a time-varying closed-loop model was used to determine the interrelationships among respiration, heart rate and blood pressure in 8 normal adults. A recursive least squares algorithm was used in combination with the Laguerre expansion technique to estimate the time-varying impulse responses of the 4 model components. We found that during arousal: 1) respiratory-cardiac coupling gain increases in nonrapid-eye movement (NREM) but not in REM sleep; 2) in both NREM and REM sleep, baroreflex gain shows an initial increase, but this is followed by a more sustained decrease below pre-arousal baseline levels, allowing sympathetic tone to be elevated over a relatively long duration; 3) the gains of other model components show increases with arousal that are consistent with the increased sympathetic modulation of systemic vascular resistance and contractility of the heart. These findings establish a normative database against which further measurements of cardiovascular arousal responses in OSAS may be compared.

Cardiorespiratory effects of endoscopic esophageal variceal sclerotherapy.

Endoscopic variceal sclerotherapy (EVS) is an effective means of controlling variceal hemorrhage, which develops as a consequence of portal hypertension. While esophageal perforation, ulceration, strictures, and mediastinitis are potential complications associated with this procedure, it is not clear whether isolated pleuropulmonary events such as pleuritis, pneumonitis, and adult respiratory distress syndrome are causally related to the EVS. Endoscopy and sedation with the attendant risk of aspiration, particularly in the background of hepatic encephalopathy, may account for some of these events. Recent controlled studies of respiratory function demonstrate that EVS as such results in minor changes in gas exchange, lung volumes, and pulmonary and systemic hemodynamics. Most pulmonary complications have been reported with the use of sodium morrhuate sclerosant. Comparative studies among different sclerosants are necessary to evaluate relative safety. Finally, there have been rare reports of myocardial ischemia and pericarditis reported in association with EVS, but these are of a transient nature. Chest symptoms, roentgenographic pleuropulmonary changes, pulmonary hemodynamics, and cardiac perturbations are transient and should not preclude offering EVS to patients with variceal hemorrhage.

Measurement of lung mechanics at different lung volumes and esophageal levels in normal subjects: Effect of posture change

Lung elastance and resistance increase in the supine posture. To evaluate the effects of change in posture on regional lung mechanics at different lung volumes, lung elastance and resistance were measured at graded volume subdivisions and three esophageal levels at seated and supine body positions, using the esophageal balloon technique. Volumes were adjusted to be the same in both postures. In general, lung elastance (both static and dynamic) tended to be higher in supine posture and uniform at all lung volumes, except at 80% vital capacity, where it increased sharply. The ratio of dynamic to static lung elastance was slightly higher at the cephalad esophageal level, where regional flow rates and relative volume expansion are lower. Lung resistance varied inversely with lung volume but was higher at corresponding volume subdivisions in the supine posture. It decreased at more cephalad esophageal levels, where volume expansion and flow are less. Thus, the increase in regional flow at low volume subdivisions (most marked in the supine position) also contributed to higher lung resistance at these volumes. These findings are explained on the basis of a combination of Newtonian physics as well as nonlinear viscoelastic properties of the lung as applied to regional flow and volume expansion.

Recent developments in the physiological assessment of sarcoidosis: clinical implications.

Purpose of reviewThis review emphasizes key findings in physiologic research of sarcoidosis reported over the past year. Recent findingsSarcoidosis, a multiorgan disease involving the formation of epithelioid-cell granulomas, is characterized by reduced lung volumes, compliance, and diffusion capacity (DLCO), and, in a small number of cases, by airflow limitation. Recent studies do not show a close relationship between changes in lung volume and radiographic stage. Fatigue and exercise limitation are characteristic of this condition, and can be assessed by health-related quality of life (HRQOL) instruments. Recent investigations have focused on the evaluation of the extent of parenchymal and nodal inflammatory activity by PET using 18F-fluorodeoxyglucose (FDG-PET imaging). Pulmonary hypertension in advanced cases of sarcoidosis contributes to increased physical impairment, and decreased HRQOL and survival. It is best associated with ambulatory desaturation, reduced DLCO, and abnormal cardiopulmonary exercise testing findings indicative of pulmonary vascular disease. If pulmonary hypertension is suspected, it should be screened for by echocardiography and confirmed by right heart catheterization. Selected patients with progressive disease unresponsive to medical therapy or with severe pulmonary hypertension should be considered for lung transplantation. Current criteria for lung transplantation include New York Heart Association functional class III–IV, pulmonary hypertension, and/or right atrial pressure at least 15 mmHg. SummaryPeriodic assessment of HRQOL measures, exercise-induced hypoxemia, and right-sided cardiac pressures for pulmonary hypertension provides, to date, the best insight into the magnitude of physiologic impairment, serving as guideposts for management (including lung transplantation) and prognosis.

Pulmonary physiology in interstitial lung disease: recent developments in diagnostic and prognostic implications

Pulmonary function changes in interstitial lung disease are characterized by loss of lung volume, increase in ratio of forced expiratory volume in 1 second to forced vital capacity, and decrease in carbon monoxide diffusion capacity. Recent developments in the assessment of respiratory mechanics in infiltrative lung disease have elucidated volume and flow dependence of lung and total respiratory resistance and elastance related to the viscoelastic properties of the respiratory system. A new, simple test of applying negative expiratory pressure at the mouth during tidal expiration can be used to generate expiratory flow-volume curves to detect flow limitation in patients with restrictive as well as obstructive disorders. This method is useful in patients who are weak, uncoordinated, or who cough during forced maneuvers. Poor prognostic signs in interstitial lung disease include male gender, paucity of lymphocytes on bronchoalveolar lavage, extensive radiographic infiltration, absence of cellular histologic findings on lung biopsy, presence of right-axis deviation, persistent or progressive decrease in lung volumes, and diffusion capacity of carbon monoxide.

Expiratory Flow Limitation in Obstructive Sleep Apnea and COPD: A Quantitative Method to Detect Pattern Differences Using the Negative Expiratory Pressure Technique

Background: Expiratory flow limitation (EFL), determined by the negative expiratory pressure (NEP) technique, can exhibit overlapping patterns in COPD, obstructive sleep apnea (OSA) and non-OSA obesity. We assessed the ability of a quantitative method to assess EFL to discriminate COPD from obese and OSA patients during NEP (-2 to -3 cm H2O) testing. Methods: EFL was quantified by measuring the area under the preceding control tidal breath (Vt) subtended by the NEP curve (%AUC). To quantify mean lost flow, the ratio of %AUC to percentage of control Vt over which EFL occurred (%EFL) (= %AUC/%EFL) was computed. Percent EFL, %AUC, and %AUC/%EFL was compared in 42 patients with COPD, 28 obese subjects without OSA, 50 with OSA (26 mild-moderate, 24 severe) and 19 control subjects, in seated and supine postures. Results: All patients exhibited %EFL values significantly higher than control subjects, corrected for age and gender (ANOVA). All but the COPD group exhibited higher %EFL while supine, but not %AUC or %AUC/%EFL. Amongst seated subjects, %EFL was highest in COPD, and amongst supine groups, it was greatest in OSA and COPD. %AUC/%EFL was significantly higher in mild-moderate OSA than in COPD only while seated. %AUC or %AUC/%EFL did not discriminate amongst other cohorts in either posture. Conclusions: Computation of %EFL helps distinguish EFL in COPD, obese and OSA patients from those of control subjects. Computation of %AUC and %AUC/%EFL is useful in determining the magnitude of extrathoracic FL in individuals with obesity and OSA, but does not distinguish between cohorts.

Microscopic pulmonary embolisation of an indwelling central venous catheter with granulomatous inflammatory response

Indwelling catheters can disintegrate into tiny fragments and embolise. Once the fragments are detected radiographically, they can be removed using vascular intervention techniques. Rarely, indwelling catheters dwindle into inextricable pieces that embolise into minute pulmonary vessels and lymphatics, causing granulomatous changes microscopically. The present study reports a 54-yr-old female who had received several indwelling central lines during several abdominal surgeries over a 5-yr period. The patient developed a noncaseating granulomatous skin lesion followed by exertional dyspnoea a few months later. Chest radiographs and computed tomography showed diffuse interstitial infiltrates. Open lung biopsy showed two types of granulomas: 1) peri-lymphangitic and peri-bronchiolar non-necrotising granulomas consistent with sarcoidosis; and 2) distinct foreign body granulomas. In some of the foreign body granulomas, confocal Raman spectroscopy identified the presence of bisphenol-A-polycarbonate, a polymer commonly used in biomedical devices. The patient improved following treatment with prednisone followed by methotrexate. The present case illustrates an interesting combination of two causes of granulomatous disease, the importance of examining all biopsy specimens from sarcoidosis patients for foreign particles and the rare occurrence of microscopic embolisation of catheter fragments to the lung with foreign-body giant cell reaction to them.