Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma.

BACKGROUND: Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations. METHODS: In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 µg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed. RESULTS: Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups. CONCLUSIONS: Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).

Respiratory considerations in patients with neuromuscular disorders.

Patients with neuromuscular disorders (NMDs) develop respiratory impairment as muscles weaken. Ensuing complications include reductions in lung volume, compliance, and cough ability and increased risk for lung infections. Sleep disordered breathing results from weakened upper airway muscles and/or impaired central ventilatory control systems. Evaluation includes measurement of seated and supine vital capacity (VC) and respiratory muscle strength. Assisted cough techniques facilitate airway clearance. The decision to initiate assisted ventilation is multifactorial, and may include consideration of patient symptoms, spirometry, pulmonary pressures, sleep studies or blood gas values. Most patients prefer noninvasive ventilation to enhance mobility and independence. Tracheostomy is indicated when bulbar function is impaired and cough assist measures fail to clear the airway. Technological advances in respiratory support have improved quality of life and longevity. Home care is the best option for most patients but remains a challenge, especially for caregivers with regard to physical, emotional, and financial implications, as well as social, administrative, and insurance concerns.

Caribbean Latinx with moderate-severe asthma bear greater asthma morbidity than other Latinx.

BACKGROUND: Hispanic/Latinx (HL) ethnicity encompasses racially and culturally diverse subgroups. Studies suggest that Puerto Ricans (PR) may bear greater asthma-related morbidity than Mexicans, but these were conducted in children or had limited clinical characterization. OBJECTIVES: This study sought to determine whether disparities in asthma morbidity exist among HL adult subgroups. METHODS: Adults with moderate-severe asthma were recruited from US clinics, including from Puerto Rico, for the Person Empowered Asthma Relief (PREPARE) trial. Considering the shared heritage between PR and other Caribbean HL (Cubans and Dominicans [C&D]), the investigators compared baseline self-reported clinical characteristics between Caribbean HL (CHL) (PR and C&D: n = 457) and other HLs (OHL) (Mexicans, Spaniards, Central/South Americans; n = 141), and between CHL subgroups (C&D [n = 56] and PR [n = 401]). This study compared asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids, emergency department/urgent care (ED/UC) visits, hospitalizations, health care utilization) through negative binomial regression. RESULTS: CHL compared to OHL were similar in age, body mass index, poverty status, blood eosinophils, and fractional exhaled nitric oxide but were prescribed more asthma controller therapies. Relative to OHL, CHL had significantly increased odds of asthma exacerbations (odds ratio [OR]: 1.84; 95% CI: 1.4-2.4), ED/UC visits (OR: 1.88; 95% CI: 1.4-2.5), hospitalization (OR: 1.98; 95% CI: 1.06-3.7), and health care utilization (OR: 1.91; 95% CI: 1.44-2.53). Of the CHL subgroups, PR had significantly increased odds of asthma exacerbations, ED/UC visits, hospitalizations, and health care utilization compared to OHL, whereas C&D only had increased odds of exacerbations compared to OHL. PR compared to C&D had greater odds of ED/UC and health care utilization. CONCLUSIONS: CHL adults, compared with OHL, adults reported nearly twice the asthma morbidity; these differences are primarily driven by PR. Novel interventions are needed to reduce morbidity in this highly impacted population.

Effect of bronchial thermoplasty on static and dynamic lung compliance and resistance in patients with severe persistent asthma.

RATIONALE: Bronchial thermoplasty (BT) reduces severity and frequency of bronchoconstriction and symptoms in severe, persistent asthmatics although it is usually not associated with change in spirometric variables. Other than spirometry. there are almost no data on changes in lung mechanics following BT. OBJECTIVE: To assess lung static and dynamic lung compliance (Cst,L and Cdyn,L, respectively) and static and dynamic lung resistance (Rst,L and Rdyn,L, respectively) before and after BT in severe asthmatics using the esophageal balloon technique. METHODS: Rdyn,L and Cdyn,L were measured at respiratory frequencies up to 145 breaths/min, using the esophageal balloon technique in 7 patients immediately before and 12-50 weeks after completing a series of 3 BT sessions. RESULTS: All patients experienced improved symptoms within a few weeks following completion of BT. Pre-BT, all patients exhibited frequency dependency of lung compliance, with mean Cdyn,L decreasing to 63% of Cst,L at maximum respiratory rates. Post-BT, Cst,L did not change significantly from pre-thermoplasty values, while Cdyn,L diminished to 62%% of Cst,L. In 4 of 7 patients, post-BT values of Cdyn,L were consistently higher than pre-BT over the range of respiratory rates. RL in 4 of 7 patients during quiet breathing and at higher respiratory frequencies decreased following BT. CONCLUSIONS: Patients with severe persistent asthma exhibit increased resting lung resistance and frequency dependence of compliance, the magnitudes of which are ameliorated in some patients following bronchial thermoplasty and associated with variable change in frequency dependence of lung resistance. These findings are related to asthma severity and may be related to the heterogeneous and variable nature of airway smooth muscle modeling and its response to BT.

Peak Quadriceps Muscle Torque and Electromyographic Output in Patients With Chronic Respiratory Disorders: Effects of Pulmonary Rehabilitation.

Objective: To assess the change in relation of the peak quadriceps electromyographic signal to the peak torque produced during a train of 5 isokinetic knee extensions (from 90 degrees below horizontal at a constant speed of 60 degrees/s) at baseline, and at 4 and 8 weeks of pulmonary rehabilitation. Design: In this prospective observational study, isokinetic contractions were recorded during the extensions from the knee bent at 90 degrees to the horizontal plane against graded resistance. Peak quadriceps torque signal (Tq) and peak electromyographic signal (Eq) were recorded by dynamometry and surface electrodes placed at designated locations over the muscle group, respectively. Setting: Physical therapy department in a tertiary care medical center. Participants: Eighteen patients (9 restrictive lung disease, 6 chronic airflow limitation, 3 non-ILD restrictive; N=18) were compared with 11 healthy control subjects. Interventions: Patients underwent an 8-week pulmonary rehabilitation program. Main Outcome Measures: Comparisons of Tq, Eq, and Tq/Eq ratio among patients and controls were by analysis of variance. Associations between physiological variables were determined by multivariable Pearson's correlation. Results: Compared with patients, controls exhibited a 22% higher baseline mean peak Eq (P<.05) and 76% higher mean peak Tq (P=.02) during knee extensions. Patients' peak Eq/Tq was twice as high as in the controls (P=.02); at 4 weeks, Eq/Tq in patients decreased by 44% (P<.04) with no further decline at 8 weeks; changes in Eq/Tq of 5 of 6 patients paralleled changes in their respective St George's Respiratory Questionnaire scores. There was no change in Tq or Eq/Tq over time among the control cohort. Conclusions: Eight weeks of pulmonary rehabilitation result in a decrease in Eq/Tq, indicating improvement in force generation of limb muscles, with the change occurring in the first 4 weeks.

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

PURPOSE OF REVIEW: This review emphasizes key findings in physiologic research of sarcoidosis reported over the past year. RECENT FINDINGS: 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. SUMMARY: 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.

Methods and Applications in Respiratory Physiology: Respiratory Mechanics, Drive and Muscle Function in Neuromuscular and Chest Wall Disorders.

Individuals with neuromuscular and chest wall disorders experience respiratory muscle weakness, reduced lung volume and increases in respiratory elastance and resistance which lead to increase in work of breathing, impaired gas exchange and respiratory pump failure. Recently developed methods to assess respiratory muscle weakness, mechanics and movement supplement traditionally employed spirometry and methods to evaluate gas exchange. These include recording postural change in vital capacity, respiratory pressures (mouth and sniff), electromyography and ultrasound evaluation of diaphragmatic thickness and excursions. In this review, we highlight key aspects of the pathophysiology of these conditions as they impact the patient and describe measures to evaluate respiratory dysfunction. We discuss potential areas of physiologic investigation in the evaluation of respiratory aspects of these disorders.

Klebsiella brain abscess in an immunocompetent patient: a case report.

BACKGROUND: Klebsiella pneumoniae brain abscesses are a rare entity and typically present in immunocompromised patients. We present a case of an overall healthy patient who developed a Klebsiella pneumoniae brain abscess in the absence of liver pathology. CASE PRESENTATION: A 46-year-old Vietnamese man with past medical history significant for hypertension presented to the hospital with acute on chronic worsening of altered mental status, personality changes, and gait dysfunction. Initial vitals revealed temperature of 37.1 °C, heart rate 87 beats/minute, blood pressure 150/87 mmHg, respiratory rate 18/minute, and oxygen saturation 99% on room air. Physical exam was notable for altered mental status, Glasgow Coma Scale (GCS) score of 14, and right lower facial droop. Cardiopulmonary exam was within normal limits. Head computed tomography (CT) showed a left frontotemporal mass, with subsequent brain magnetic resonance imaging (MRI) revealing a ring-enhancing lesion concerning for a brain abscess. The abscess was urgently drained; however, there was intraoperative spillage into the ventricles. Intraoperative cultures grew Klebsiella pneumoniae, and the patient was maintained on appropriate antibiotics. He developed worsening mental status, septic shock, and cerebral edema requiring decompressive left hemicraniectomy. Computed tomography of the abdomen and pelvis revealed no hepatic lesions. The patient did not improve, and the family elected for comfort measures. CONCLUSION: High mortality is associated with Klebsiella pneumoniae (as opposed to Klebsiella oxytoca) brain abscesses, especially in the setting of intraventricular spread. This case illustrates the need for early detection, and an aggressive medical and surgical treatment approach is required for a potential favorable outcome.

A randomized, open-label, pragmatic study to assess reliever-triggered inhaled corticosteroid in African American/Black and Hispanic/Latinx adults with asthma: Design and methods of the PREPARE trial.

BACKGROUND: Asthma prevalence, morbidity, and mortality disproportionately impact African American/Black (AA/B) and Hispanic/Latinx (H/L) communities. Adherence to daily inhaled corticosteroid (ICS), recommended by asthma guidelines in all but the mildest cases of asthma, is generally poor. As-needed ICS has shown promise as a patient-empowering asthma management strategy, but it has not been rigorously studied in AA/B or H/L patients or in a real-world setting. Design and Aim The PeRson EmPowered Asthma RElief (PREPARE) Study is a randomized, open-label, pragmatic study which aims to assess whether a patient-guided, reliever-triggered ICS strategy called PARTICS (Patient-Activated Reliever-Triggered Inhaled CorticoSteroid) can improve asthma outcomes in AA/B and H/L adult patient populations. In designing and implementing the study, the PREPARE research team has relied heavily on advice from AA/B and H/L Patient Partners and other stakeholders. Methods PREPARE is enrolling 1200 adult participants (600 AA/Bs, 600H/Ls) with asthma. Participants are randomized to PARTICS + Usual Care (intervention) versus Usual Care (control). Following a single in-person enrollment visit, participants complete monthly questionnaires for 15 months. The primary endpoint is annualized asthma exacerbation rate. Secondary endpoints include asthma control; preference-based quality of life; and days lost from work, school, or usual activities. Discussion The PREPARE study features a pragmatic design allowing for the real-world assessment of a patient-centered, reliever-triggered ICS strategy in AA/B and H/L patients. Outcomes of this study have the potential to offer powerful evidence supporting PARTICS as an effective asthma management strategy in patient populations that suffer disproportionately from asthma morbidity and mortality.

Thoracic gunshot wounds: alterations to pulmonary function and respiratory muscle strength.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Circulating angiotensin peptides levels in Acute Respiratory Distress Syndrome correlate with clinical outcomes: A pilot study.

RATIONALE: We propose renin angiotensin system (RAS) peptides are critical in wound reparative processes such as in acute respiratory distress syndrome (ARDS). Their role in predicting clinical outcomes in ARDS has been unexplored; thus, we used a targeted metabolomics approach to investigate them as potential predictors of outcomes. METHODS: Thirty-nine ARDS patients were enrolled within 24 hours of ARDS diagnosis. Plasma RAS peptide levels were quantified at study entry and 24, 48 and 72 hours using a liquid chromatography-mass spectrometry based metabolomics assay. RAS peptide concentrations were compared between survivors and non-survivors, and were correlated with clinical and pulmonary measures. MEASUREMENTS AND MAIN RESULTS: Angiotensin I (Ang-I or A(1-10)) levels were significantly higher in non-survivors at study entry and 72 hours. ARDS survival was associated with lower A(1-10) concentration (OR 0.36, 95% CI 0.18-0.72, p = 0.004) but higher A(1-9) concentration (OR 2.24, 95% CI 1.15-4.39, p = 0.018), a biologically active metabolite of A(1-10) and an agonist of angiotensin II receptor type 2. Survivors had significantly higher median A(1-9)/A(1-10) and A(1-7)/A(1-10) ratios than the non-survivors (p = 0.001). Increased A(1-9)/A(1-10) ratio suggests that angiotensin converting enzyme II (ACE2) activity is higher in patients who survived their ARDS insult while an increase in A(1-7)/A(1-10) ratio suggests that ACE activity is also higher in survivors. CONCLUSION: A(1-10) accumulation and reduced A(1-9) concentration in the non-survivor group suggest that ACE2 activities may be reduced in patients succumbing to ARDS. Plasma levels of both A(1-10) and A(1-9) and their ratio may serve as useful biomarkers for prognosis in ARDS 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.

Tracheobronchomalacia and tracheal hemorrhage in patients with Duchenne muscular dystrophy receiving long-term ventilation with uncuffed tracheostomies.

STUDY OBJECTIVES: Autopsy evaluation of tracheobronchomalacia (TBM) in patients with Duchenne muscular dystrophy (DMD) who were receiving long-term ventilation through uncuffed tracheostomies. DESIGN: 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. SETTING: Rehabilitation facility affiliated with a university medical center. RESULTS: 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. CONCLUSIONS: 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.

Extrathoracic expiratory flow limitation in obesity and obstructive and restrictive disorders: effects of increasing negative expiratory pressure.

BACKGROUND: 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. PURPOSE: 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. SUBJECTS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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 H(2)O) 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.

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. OBJECTIVES: To assess relationship of fatigue in sarcoidosis with PCLs at rest and with cardiopulmonary exercise testing (CPET). METHODS: We assessed lung function, CPET data, multidimensional fatigue inventory, plasma tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) concentrations before, immediately after, and 4-6 h following CPET in 22 sarcoidosis patients (13 receiving immunomodulatory drugs) and 22 controls. RESULTS: 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-1ß levels did not differ between cohorts. Patients exhibited a 28% increase (statistically not significant) in TNF-α level immediately post exercise. Plasma IL-ß 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-1ß correlated with physical fatigue, reduced motivation and total fatigue; TNF-α levels only correlated with general fatigue score. CONCLUSION: Treated sarcoidosis patients exhibit a relation between physical fatigue, reduced motivation and total fatigue and pre-exercise plasma IL-1ß 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.