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Rationale: Survival and longevity in patients with cystic fibrosis (CF) have improved with new treatments, so that pregnancy can be safely undertaken despite physiologic limitations. Dyspnea still develops in the latter stages of pregnancy. To explain this symptom, we evaluated the effect of pregnancy on lung function before and after delivery. Methods: Records of 23 pregnant patients with CF were retrospectively reviewed for data analysis. Spirometry was recorded prior to pregnancy, at first and third trimesters, and every three months following delivery up to one year. Comparisons between time points were adjusted for age and pre-gestational BMI by analysis of variance (ANOVA). Results: Complete clinical and spirometric data were available for eleven of these patients (13 pregnancies total), obtained between 2009 and 2017. FEV1 and FVC declined significantly from baseline to third trimester (by 8.1%, p Conclusions: The changes in FEV1 and FVC occur as a result of increases in intravascular blood volume and lung water during the third trimester. At the same time, FEV1/FVC increases as there is reversal of bronchiolar constriction with elimination of extracellular fluid and lung water. Furthermore, restoration of end-expiratory lung volume post-partum counteracts reversal of air trapping with resolution of peribronchiolar edema, with FVC remaining unchanged. These changes would explain decrease in dyspnea following delivery in CF patients.

Background: Tidal expiratory flow limitation (tEFL) is defined as absence of increase in air flow during forced expiration compared to tidal breathing and is related to dyspnea at rest and minimal exertion in patients with chronic airflow limitation (CAL). Tidal EFL has not been expressed as a continuous variable (0% - 100%) in previous analyses. Objective: To relate the magnitude of tEFL to spirometric values and Modified Medical Research Council (MMRC) score and Asthma Control Test (ACT). Methods: Tidal EFL was computed as percent of the tidal volume (0% - 100%) spanned (intersected) by the forced expiratory-volume curve. Results: Of 353 patients screened, 192 (114 M, 78 F) patients (136 with COPD, 56 with asthma) had CAL. Overall characteristics: (mean ± SD) age 59 ± 11 years, BMI 28 ± 7, FVC (% pred) 85 ± 20, FEV1 (% pred) 66 ± 21, FEV1/FVC 55% ± 10%, RV (% pred) 147 ± 42. Tidal EFL in patients with tEFL was 53% ± 39%. Using univariate analysis, strongest correlations were between tEFL and FVC and between tEFL and RV in patients with BMI 2. In patients with nonreversible CAL, tEFL was positively associated with increasing MMRC, negatively with spirometric measurements, and positively with RV/TLC. In asthmatics, ACT scores were higher in patients with mean BMI ≥ 28 kg/m2 (p 40% (p Conclusions: Dyspnea is strongly associated with tEFL and lung function, particularly in patients with nonreversible CAL. Air trapping and BMI contribute to tEFL.

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.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.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.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.).

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.This study sought to determine whether disparities in asthma morbidity exist among HL adult subgroups.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 [Camp;D]), the investigators compared baseline self-reported clinical characteristics between Caribbean HL (CHL) (PR and Camp;D: n = 457) and other HLs (OHL) (Mexicans, Spaniards, Central/South Americans; n = 141), and between CHL subgroups (Camp;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.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 Camp;D only had increased odds of exacerbations compared to OHL. PR compared to Camp;D had greater odds of ED/UC and health care utilization.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.

Background: The severity of COPD is commonly assessed by the reduction in forced expiratory volume at one second (FEV1), although more recently prognostic factors influencing survival have also incorporated functional capacity, degree of breathlessness on exertion, and body mass index. Increasingly, the reliability of physiological parameters such as FEV1 to predict patient-centered outcomes has been brought into question. Objectives: To evaluate the relationship between dyspnea as assessed by the Modified Medical Council Dyspnea (MMRC) scale, the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) staging and indices of lung hyperinflation and spirometry. Methods: Data were retrospectively analyzed at a 600-bed tertiary care center including spirometry, plethysmographic lung volumes, single breath carbon monoxide diffusion capacity and dyspnea graded according to MMRC, and GOLD staging. Results: Data for 331 patients were analyzed. Differences amongst FEV1, IC, IC/TLC, FRC and RV/TLC were significant between GOLD I/II and GOLD III/IV groups. The closest relationship to GOLD staging was seen with FEV1, FVC and slow vital capacity (SVC). FEV1/FVC, IC, and IC/TLC were inversely associated with MMRC score, while RV/TLC exhibited a positive relation with MMRC score. Conclusions: Indices of lung hyperinflation are closely associated, with dyspnea as assessed by MMRC grading with TLC, RV/TLC and IC exhibiting the closest relations, more so than FEV1. GOLD staging also shows strong correlations with lung volume subdivisions (weakly with TLC), more so than with FEV1. That TLC changed little between GOLD stages can be explained by the presence of collateral interalveolar channels and population characteristics different from those of other studies. These findings further support the concept that more than a reduction in FEV1, lung hyperinflation contributes to the sensation of dyspnea in airflow limitation.

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.

RationaleWe 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.MethodsThirty-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 resultsAngiotensin 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.ConclusionA(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.

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.

Rationale: Inspiratory muscle endurance as expressed by the tension-time index of the diaphragm [TTI=(Pdi/ Pdimax) × (Ti/Ttot)] in normal subjects and cardiorespiratory disorders requires the use of esophageal and gastric balloons. A noninvasive technique can be used in which the ratio of tidal volume to vital capacity (Vt/VC) is substituted for Pdi/Pdimax, with the resulting relationship [(Ti/Ttot) × (Vt/FVC)] called the breathing intolerance index (BIT). The response to medical management of BIT in patients with cardiomyopathy with chronic heartfailure has not been assessed before and after medical management. Objectives: To compare control of ventilation and BIT in patients with stable dilated cardiomyopathy at rest and exercise, and to analyze BIT, oxygen uptake and carbon dioxide elimination at baseline and approximately one year after initiating medical management. Methods: Control of ventilation and BIT were assessed in 24 patients (mean age 55.5 years; 17 males) at rest and at peak exercise during bicycle ergometry, at baseline and approximately 14 months later. Results: Median peak VO2 was 12.9 mL/kg/min and 14.3 mL/kg/min at baseline and followup, respectively (p

Rationale: Diaphragmatic tension-time index [TTdi = (Pdi/Pdimax)(Ti/ Ttot)] assesses inspiratory muscle endurance during rest and exercise. However, the procedure is invasive and not practical for general use. Recently, Tidal Volume/Vital Capacity (Vt/VC) has been substituted for Pdi/Pdimax, to assess need for assisted ventilation in chronic respiratory disorders. This technique has not been used to assess respiratory muscle endurance in other conditions during rest and exercise. Objective: To compare control of ventilation and BIT in cardiorespiratory disorders and controls and to assess their relation to oxygen uptake (V’O2) and annual acute decompensations. Methods: BIT and V’O2 were assessed in patients with stable CVD (n = 20), RD (n = 20) and C (n = 20) during bicycle ergometry. ANOVA assessed differences in variables amongst cohorts at rest and peak exercise. Results: Resting BIT was [median (25th, 75th percentiles)] 0.06 (0.04, 0.07), 0.06 (0.04, 0.09) and 0.04 (0.03, 0.05) for CVD, COPD and controls, respectively. Compared to resting, BIT increased by 3.0- to 4.6- fold at peak exercise in all cohorts (p < 0.0001). V’O2max exceeded resting values by 7.5-, 4.6-, and 9.4- fold in COPD, CVD and C, respectively (all p < 0.0001). When corrected for BIT (V’O2/BIT), controls exhibited significantly greater (V’O2/BIT) max than CVD and COPD (p < 0.0001). Amongst patients who acutely decompensated, BIT was higher only in resting CVD patients (p < 0.019). Conclusions: BIT is useful for evaluating respiratory muscle effort during rest and exercise in CVD and COPD. Oxygen uptake fails to increase in proportion to BIT in these conditions as much as in controls, reflecting impaired oxygen utilization. Its potential usefulness in predicting acute decompensations should be assessed in larger prospective studies.

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.

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-1β (IL-1β) 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-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. Conclusion: 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. Please cite this paper as: Baydur A, Alavy B, Nawathe A, Liu S, Louie S and Sharma OP. Fatigue and plasma cytokine concentrations at rest and during exercise in patients with sarcoidosis. Clin Respir J 2011; 5: 156–164.

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.

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 H2O, 10 cm H2O, and 15 cm H2O 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 H2O (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 5c m H 2O. 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 H2O, 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 H2O, 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 2004; 125:98 –105)

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.

Effects of Sleep Deprivation on Exhaled Nitric Oxide Concentrations in Medical Residents Taking Night Call Background: Exhaled nitric oxide (eNO) is considered a biomarker for airway inflammation, and has been studied most extensively in asthma. It has also been implicated as a biomarker in other forms of stress, including psychological, although results have been variable. Sleep deprivation in medical residents on duty can be stressful. Objective: The purpose of this study was to determine whether sleep deprivation was linked to altered levels of eNO and, if so, whether eNO concentrations (FeNO) could be reliably used as a simple, non-invasive measure of inflammation in varying degrees of sleep deprivation. Our hypothesis was that FeNO levels are higher during sleep deprivation. Given that taking night call can be a stressful situation (leading to sleep disruption), we asked (1) what is the relationship between FeNO in physician trainees and sleep deprivation, and (2) can FeNO be viewed as a marker for inflammation in sleep deprivation during on-call duty?

Application of the NEP technique provides a simple, rapid, non-invasive, and reliable test to detect tidal expiratory flow limitation; b) it does not require a body-box or cooperation on the patient’s part; c) it can be applied in any posture, during mechanical ventilation, and during exercise; d) it provides new insights into the physiology and pathophysiology of sev‐ eral diseases and the symptom of dyspnea.

Background: Forced Vital Capacity (FVC) has been used to assess respiratory muscle strength in patients with Neuromuscular Disease (NMD). However, postural changes to FVC have not been assessed in relation to the start of Non-Invasive Ventilation (NIV). This study aims to assess the changes to postural FVC for indications of NIV. Methods: The records of spirometry performed in seated and supine posture were retrospectively reviewed in 33 patients with NMD [18 breathing spontaneously (SB), 15 receiving NIV]. The change in FVC (in L) between seated (sit) and supine (sup) positions was expressed as %⊗ FVC (sit – sup) = [{FVC(L)sit – FVC(L)sup}/FVC(L)sit]. The postural change in forced expiratory flow (FEF), % FEF (sit – sup) was similarly computed. Results: %ΔFVC (sit – sup) in patients receiving NIV exceeded the %ΔFVC (sit – sup) of SB patients by 14-fold (p = 0.001). %ΔFEF (sit–sup) however, did not reach statistical significance between cohorts. There was a negative correlation between %ΔFVC (sit-sup) and FVCsit(% pred) (R = -0.40, p = 0.02), and a direct correlation between %ΔFVC(sit-sup) and %ΔFEF(sit-sup) (R = 0.72, p

To determine the contributions of (1) chest wall (Pcw) and (2) lung elastic recoil pressure (PL) to (3) total elastic recoil pressure exerted by the respiratory system (Prs) in 18 patients (12 men) aged 66 +/- 6 years (mean +/- 1 SD) with severe emphysema who underwent video-assisted thoracoscopic bilateral lung volume reduction surgery under paralyzed (vecuronium) general anesthesia (isoflurane).We measured preoperative and 6-week postoperative lung function studies, and intraoperative inspiratory lung conductance (GL), PL, Pcw, and Prs (cm H2O) at end-expiratory lung volume (EELV), EELV plus 0.60 +/- 0.0 L, and EELV plus 1.15 +/- 0.0 L. All values are mean +/- SEM.Preoperative vs postoperative FVC was 1.9 +/- 0.1 L vs 2.3 +/- 0.1 L (p = 0.03); FEV1 was 0.6 +/- 0.1 L vs 0.9 +/- 0.1 L (p0.02); total lung capacity was 7.4 +/- 0.4 L vs 5.9 +/- 0.3 L (p0.001); functional residual capacity was 5.7 +/- 0.4 L vs 4.4 +/- 0.2 L (p = 0.001). At EELV preoperative vs postoperative, PL was 0.0 +/- 0.3 vs 1.1 +/- 0.05 (p = 0.04), Pcw was 5.0 +/- 0.7 vs 2.4 +/- 0.9 (p = 0.02), and Prs was 5.0 +/- 0.8 vs 3.5 +/- 0.7 (p = 0.08). AT EELV plus 0.60 L, PL was 3.2 +/- 0.6 vs 6.1 +/- 0.9 (p0.001), Pcw was 8.8 +/- 0.8 vs 7.0 +/- 0.9 (p = 0.12), and Prs was 12.0 +/- 0.8 vs 13.1 +/- 0.7 (p = 0.80). At EELV plus 1.15 L, PL was 6.8 +/- 0.9 vs 10.3 +/- 1.1 (p0.001), Pcw was 13.5 +/- 1.0 vs 11.2 +/- 1.2 (p = 0.12), and Prs was 20 +/- 1.2 vs 21.5 +/- 1.0 p = 0.93). AT EELV plus 0.06 L, GL was 0.09 +/- 0.00 L/S/cm H2O vs 0.16 +/- 0.01 (p0.01). At EELV plus 1.15 L, GL was 0.12 +/- 0.01 vs 0.21 +/- 0.03 (p0.05) with similar preoperative vs postoperative GL/PL slopes.The increase in PL and decrease in Pcw following LVRS for emphysema may be responsible for the increase in spirometry and airway conductance.

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.

The passive relaxation single-breath technique has been used primarily in anesthetized human subjects to measure total respiratory system elastance and resistance. This method was used to assess the pressure-flow characteristics in 32 relaxed, conscious patients with restrictive respiratory disorders (20 with neuromuscular disease, 12 with sarcoidosis) and 27 similarly aged control subjects free of cardiothoracic disease. Using Rohrer's pressure-flow relationship during passive expiration, P/ V ˙ =K1+K2 V ˙ considerable curvilinear pressure-flow characteristics were found in both groups. These can be attributed to a combination of the upper airway and viscoelastic and elastoplastic behavior of the respiratory system. Despite the greater elastic recoil pressure (and respiratory elastance) of the restrictive patients, their pressure-flow characteristics were similar to those of the control subjects. These findings imply structural similarities in at least the lower airways, or in the effects of retractile forces along airways compensating for reduced lung volumes.

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.

Granulomatous involvement of skeletal muscle occurs in 50 to 80 percent of patients with sarcoidosis. How this may affect respiratory muscle function in sarcoidosis is not known. To attempt to answer this question, we compared respiratory function and muscle force generation, and control of ventilation in 12 untreated patients with 12 healthy, nonsmoking subjects. While seated, room air breathing, measurements included expiratory reserve volume (ERV), components of breathing pattern, and occlusion pressure at 1 s (P0.1). Three of nine patients who consented to muscle biopsy demonstrated granulomatous involvement on histologic examination, and Pmax values less than the group mean; however, some patients without muscle granulomas also demonstrated low Pmax values. Breathing pattern in the sarcoid patients was rapid and shallow, but not related to the degree of radiographic infiltration or respiratory elastance. Mean inspiratory flow (VT/TI), minute ventilation, and P0.1 were, in general, greater than in the control subjects, indicating an increase in central drive. There was a significant inverse correlation between FVC and P0.1, and a weak inverse relationship between ERV and P0.1. With no significant difference between group "effective impedances" (P0.1/(VT/TI)), findings indicate that in the sarcoidosis group, decreased muscle force generation was compensated for by an increase in central drive. Granulomatous infiltration may be one of many factors contributing to respiratory muscle weakness in sarcoidosis.

The purpose of this work is to review the use of long-term tracheal intermittent positive pressure ventilation (TIPPV) and its advantages and complications in the long-term management of neuromuscular ventilatory failure. Over 500 such individuals have been described who have had prolonged survival due largely to long-term TIPPV. Many of these individuals have remained active both professionally and socially. Long-term TIPPV is generally well tolerated and may become necessary to prolong the survival of individuals who already use noninvasive methods of ventilatory support but whose conditions have progressed to the point of requiring a tracheostomy.

To assess the relationship between respiratory mechanics and muscle strength and control of ventilation in patients with neuromuscular disease (NMD), we compared PImax and PEmax at RV, FRC and TLC, total respiratory elastance (Ers) with VT, TI, TT, VE, VT/TI, TI/TT, P.01, and P.01/(VT/TI) effective impedance in 21 patients with NMD and 21 healthy control (C) subjects, in seated position breathing room air. Ers in NMD patients was 79 percent higher than in the C subjects. While TI, TT, and VT in NMD were approximately half the corresponding C values, P.01 was 66 percent greater than in the C subjects (both p less than 0.001). NMD PImax and PEmax ranged from 37 to 52 percent of corresponding C values, respectively. Despite significant respiratory muscle weakness, only 7 of 16 patients demonstrated a PaCo2 greater than 45 mm Hg. Ventilatory output in NMD was modulated by respiratory mechanics as indicated by the increased P.01. In spite of muscle weakness, central drive in patients with NMD is not decreased, and in fact, is often increased. VE is not an accurate measure of central drive because of abnormal intrinsic respiratory mechanics and the effects of conscious responses or reflexes.

To our knowledge, the effects of corrective spinal surgery on total respiratory mechanics and its components in anesthetized patients with kyphoscoliosis have not been previously reported in detail. We studied 13 patients with kyphoscoliosis; their mean (± SD) age was 24.7 ± 2.1 years; eight underwent anterior and posterior spinal fusions (AF and PF, respectively) two weeks apart (group A), four underwent PF alone (group B), and one had a three-stage procedure. Mean total respiratory elastance (Ers), static and dynamic lung elastance (Est,L and Edyn,L, respectively), chest wall elastance (Ew), and lung resistance (RL) were derived according to previously described methodology. In group A, Ers and Ew increased by 39 percent and 58 percent, respectively, following AF and by 20 percent and 129 percent following PF, while Est,L and Edyn,L did not change or declined following PF. Lung resistance increased 19 percent and 41 percent by the end of AF and PF, respectively, in group A. In group B, Ew more than doubled, resulting in a 39 percent increase in Ers. Increases in Ers, Ew, and respiratory flow resistance observed at the time of spinal corrective surgery for kyphoscoliosis may result from rib cage trauma and changes in airway caliber related to microatelectasis and uneven distribution of mechanical properties within the lungs. Spinal correction results in immediate and short-term deterioration of respiratory mechanics measured under anesthesia.

We present 17 patients with advanced DMD who required long-term assisted ventilation. Eleven patients used part-time assisted ventilation. Five of the patients received BV and/or M-IPPV or N-IPPV between two and nine years before requiring full-time T-IPPV, while six others initially used part-time T-IPPV. One patient used all three modes before requiring full-time T-IPPV. Mean (+/- SD) FVC and rebreathe PCO2 at the outset of assisted ventilation were 0.62 +/- 0.20 L and 47.4 +/- 7.5 mm Hg, respectively. Clinical features were divided between symptoms suggesting respiratory muscle fatigue and sleep-related disordered breathing. We found that, while useful in early respiratory insufficiency, BV is associated with recurrent aspiration. In our experience, N-IPPV offers the safest and most convenient form of noninvasive ventilation. When the VC has decreased to about 300 ml, most patients will require full-time ventilation; T-IPPV is advised to provide airway access to suction secretions.