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Ahmet Baydur
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ABSTRACT: This review emphasizes key findings in physiologic research of sarcoidosis reported over the past year.
Sarcoidosis, a multiorgan disease involving the formation of epithelioid-cell granulomas, is characterized by reduced lung volumes, compliance, and diffusion capacity (D(L)CO), 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 D(L)CO, 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.
Periodic 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.
Current opinion in pulmonary medicine 07/2012; 18(5):499-505. · 3.08 Impact Factor
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ABSTRACT: 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.
To assess relationship of fatigue in sarcoidosis with PCLs at rest and with cardiopulmonary exercise testing (CPET).
We assessed lung function, CPET data, multidimensional fatigue inventory, plasma tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations before, immediately after, and 4-6 h following CPET in 22 sarcoidosis patients (13 receiving immunomodulatory drugs) and 22 controls.
Patients exhibited greater fatigue, reduced cardiorespiratory function, higher Medical Research Council (MRC) scores and higher plasma TNF-α concentrations than controls at all times. Plasma IL-1β levels did not differ between cohorts. Patients exhibited a 28% increase (statistically not significant) in TNF-α level immediately post exercise. Plasma IL-β concentrations did not change among cohorts. Treated patients exhibited higher MRC and physical fatigue scores and lower breathing reserve, but no differences in cardiorespiratory function or PCLs compared to untreated patients. In treated patients, pre-exercise plasma IL-1β correlated with physical fatigue, reduced motivation and total fatigue; TNF-α levels only correlated with general fatigue score.
Treated sarcoidosis patients exhibit a relation between physical fatigue, reduced motivation and total fatigue and pre-exercise plasma IL-1β concentrations. Acute exercise does not increase PCLs. Whether the reduced MRC score and physical fatigue in treated patients is related to the therapy or to the underlying inflammatory process is difficult to determine.
The Clinical Respiratory Journal 07/2011; 5(3):156-64. · 1.06 Impact Factor
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ABSTRACT: The impact on respiratory function of gunshot injuries to the chest is unknown. The objective is to assess pulmonary function and respiratory muscle strength (RMS) in patients who have recently sustained an isolated gunshot injury to the chest.
After institutional review board approval, patients with isolated gunshot injuries to the chest were prospectively identified. Study patients underwent pulmonary function testing and an assessment of RMS and gas exchange.
Ten male patients sustaining an isolated pulmonary gunshot wound were prospectively enrolled with a mean age of 29 years ± 10 years and mean Injury Severity Score of 15 ± 5. All patients had an associated pneumothorax (n = 1), hemothorax (n = 4), or a combination of both (n = 5). After removal of all thoracostomy tubes and before discharge [7.4 days ± 5.4 days (range, 2-21 days)], patients underwent respiratory function testing. Lung volume subdivisions were reduced by 25% to 60% of predicted and diffusion capacity by 37% with preservation of the normal ratio of diffusion capacity to alveolar volume. In the six subjects able to perform spirometry in seated and supine postures, forced vital capacity decreased by 20% when changing posture (p = 0.046). Arterial blood gas analysis showed significant reduction in the P(AO)₂/FIO₂ ratio (or increase in AaDO₂). Maximal respiratory pressures were severely reduced from predicted values, the maximal inspiratory pressure by 60% and the maximal expiratory pressure by 78%.
Lung volumes and RMS are decreased moderately to severely in patients who have sustained an isolated pulmonary gunshot wound. Expiratory muscle force generation is more severely affected than inspiratory muscle force. Further investigation of the long-term impact of these injuries on respiratory function is warranted.
The Journal of trauma 10/2010; 69(4):756-60. · 2.48 Impact Factor
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Ahmet Baydur
Chest 06/2008; 133(5):1062-3. · 5.25 Impact Factor
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ABSTRACT: 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.
Annals of Biomedical Engineering 09/2007; 35(8):1425-43. · 2.37 Impact Factor
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ABSTRACT: 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.
IEEE Transactions on Biomedical Engineering 02/2006; 53(1):74-82. · 2.28 Impact Factor
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Chest 11/2004; 126(4):1390-2. · 5.25 Impact Factor
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ABSTRACT: The negative expiratory pressure (NEP) technique is used to detect intrathoracic expiratory flow limitation (EFL) in patients with respiratory disorders. Application of NEP may result in a sustained decrease of flow below control as a result of upper airway collapse, which may invalidate interpretation of the test. This response to NEP is common in patients with obstructive sleep apnea syndrome (OSAS). The prevalence of this phenomenon, however, has not been studied in healthy subjects and patients with obstructive and restrictive disorders without OSAS.
The purpose of this study was as follows: (1) to assess the effects of increasing NEP levels on upper airway patency, and (2) to determine the factors that predispose to intrathoracic flow limitation or upper airway collapse during NEP application in different postures in healthy nonobese and obese subjects, and in patients with obstructive and restrictive respiratory disorders.
Fifty-six patients with obstructive airway disease (21 patients with COPD, 16 patients with simple chronic bronchitis, and 19 patients with asthma) were compared with 47 patients with restrictive respiratory disorders, 20 nonobese and healthy subjects, and 9 obese subjects (body mass index > 30) without a history of snoring or OSAS.
NEP at levels of 5 cm H(2)O, 10 cm H(2)O, and 15 cm H(2)O were applied at the mouth immediately after the onset of tidal expiration while seated and supine. Intrathoracic EFL was defined as no change in expiratory flow over any portion of the immediately preceding control breath. Upper airway collapse or narrowing was detected when flows decreased below those of the control breath.
Ten patients (18%) with obstructive airway disease (7 patients with COPD) exhibited EFL at NEP of 5 cm H(2)O (4 patients were supine only, and 6 patients were both supine and sitting). No patient with restrictive disorders or healthy obese and nonobese subjects presented EFL at NEP of 5 cm H(2)O. In almost all subgroups, both seated and supine, subjects exhibited a transient decrease of flow below control immediately after the application of NEP in occasional breaths. As NEP increased, the number of subjects who exhibited this response in occasional breaths declined, while the number of subjects who displayed this pattern in all breaths increased. Conversely, there were very few subjects in each subgroup who exhibited a sustained decrease in flow below control in occasional breaths at NEP at 5 cm H(2)O, and only one healthy obese subject who displayed this response in all breaths in supine position only.
In general, an increase in NEP resulted in only rare instances of sustained decrease in flow below control in all breaths. While transient decreases in flow exhibited immediately after the onset of NEP in all breaths are common and become more prevalent as NEP is increased beyond 5 cm H(2)O, there are only rare instances of sustained decrease in flow below control throughout expiration at all levels of NEP tested, indicating an appropriate upper airway dilator response that maintains patency. Thus, in subjects without OSAS, assessment of intrathoracic EFL with NEP is valid in almost all instances.
Chest 02/2004; 125(1):98-105. · 5.25 Impact Factor
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ABSTRACT: Autopsy evaluation of tracheobronchomalacia (TBM) in patients with Duchenne muscular dystrophy (DMD) who were receiving long-term ventilation through uncuffed tracheostomies.
Necropsies were performed in seven patients with DMD who had received positive-pressure ventilation through uncuffed tracheostomies for a duration of 5 to 30 years.
Rehabilitation facility affiliated with a university medical center.
The range of peak airway pressures sustained during ventilation by all the patients was 23 mm Hg to 36 mm Hg. Bronchoscopy (which was performed in four of the five patients) detected tracheomalacia in only one of the patients. Five of the seven patients demonstrated variable degrees of airway malacia. Two patients also had tracheal perforations, one of which resulted in a fatal hemorrhage from a tracheovascular fistula.
Given enough time, patients receiving positive-pressure ventilation can develop airway thinning and dilation even without the use of an inflated tracheostomy cuff. There is also a potential for tracheal erosion into an adjacent artery that can lead to fatal hemorrhage. Such findings also have implications for individuals receiving noninvasive positive-pressure ventilation, who could develop TBM as a result of the continuous cycling pressures on the airway wall.
Chest 05/2003; 123(4):1307-11. · 5.25 Impact Factor
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ABSTRACT: Respiration, R-R interval, blood pressure, and other polysomnographic variables were recorded in eight normal subjects and nine patients with untreated obstructive sleep apnea syndrome in wakefulness and sleep. To increase respiratory and cardiovascular variability, a computer-controlled ventilator delivered randomly modulated inspiratory pressures that were superimposed on a baseline continuous positive airway pressure. A mathematical model allowed heart rate variability to be partitioned into a component mediated by respiratory-cardiac coupling and one mediated by the baroreflexes. Respiratory-cardiac coupling gain was lower in patients versus normal subjects (36.9 +/- 3.3 versus 66.1 +/- 5.6 milliseconds L-1, p < 0.03). Baroreflex gain in patients was also depressed relative to normal subjects (2.3 +/- 0.4 versus 4.9 +/- 0.7 milliseconds mm Hg-1; p < 0.02). Baroreflex gain increased two- to threefold from wakefulness to sleep in normal subjects, but was relatively unaffected by state change in patients. Along with results derived from spectral analysis of cardiovascular variability, these findings confirm previous reports that obstructive sleep apnea syndrome is associated with reduced parasympathetic and elevated sympathetic activity. The model-based approach provides a more precise characterization of heart rate variability that can be employed in conjunction with spectral analysis for the noninvasive detection and assessment of autonomic cardiovascular abnormality in obstructive sleep apnea syndrome.
American Journal of Respiratory and Critical Care Medicine 01/2003; 167(2):128-36. · 11.08 Impact Factor
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Ahmet Baydur
Chest 03/2002; 121(2):324-6. · 5.25 Impact Factor
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Respiration 02/2002; 69(2):165. · 2.26 Impact Factor
