The Regulation of Fatty Acid Synthase by Exosomal miR-143-5p and miR-342-5p in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease caused by an aberrant repair of injured alveolar epithelial cells. The maintenance of the alveolar epithelium and its regeneration after the damage is fueled by alveolar type II (ATII) cells. Injured cells release exosomes containing microRNAs (miRNAs), which can alter the recipient cells' function. Lung tissue, ATII cells, fibroblasts, plasma, and exosomes were obtained from naive patients with IPF, patients with IPF taking pirfenidone or nintedanib, and control organ donors. miRNA expression was analyzed to study their impact on exosome-mediated effects in IPF. High miR-143-5p and miR-342-5p levels were detected in ATII cells, lung tissue, plasma, and exosomes in naive patients with IPF. Decreased FASN (fatty acid synthase) and ACSL-4 (acyl-CoA-synthetase long-chain family member 4) expression was found in ATII cells. miR-143-5p and miR-342-5p overexpression or ATII cell treatment with IPF-derived exosomes containing these miRNAs lowered FASN and ACSL-4 levels. Also, this contributed to ATII cell injury and senescence. However, exosomes isolated from patients with IPF taking nintedanib or pirfenidone increased FASN expression in ATII cells compared with naive patients with IPF. Furthermore, fibroblast treatment with exosomes obtained from naive patients with IPF increased SMAD3, CTGF, COL3A1, and TGFß1 expression. Our results suggest that IPF-derived exosomes containing miR-143-5p and miR-342-5p inhibited the de novo fatty acid synthesis pathway in ATII cells. They also induced the profibrotic response in fibroblasts. Pirfenidone and nintedanib improved ATII cell function and inhibited fibrogenesis. This study highlights the importance of exosomes in IPF pathophysiology.

Physiologic correlates of sleep quality in severe emphysema.

BACKGROUND: Sleep quality is poor in severe emphysema. We hypothesized that in addition to nocturnal oxygen desaturation, the severity of airflow obstruction and degree of thoracic hyperinflation are responsible. METHODS: Twenty-five patients (14 males, 64 ± 6 [ ± SD] yrs, BMI 24.7 ± 4.2 kg/m(2)) with severe emphysema (FEV(1) = 28 ± 8% predicted, TLC = 125 ± 14% predicted) were studied. Measurements included spirometry, lung volumes, arterial blood gas, length of the diaphragm's zone of apposition (LZAP) and a polysomnogram. RESULTS: Total sleep time (TST) was 227 ± 93 minutes with a sleep efficiency (SE) of 56 ± 21%. The mean SaO(2), lowest SaO(2), and% TST with a SaO(2) < 90% were 90 ± 5%, 83 ± 8% and 29 ± 40%, respectively. TST correlated with FEV(1)% (r = 0.5, p = 0.02), FVC% (r = 0.4, p = 0.03) and LZAP (r = 0.5, p = 0.01). SE correlated with FEV(1)% (r = 0.5, p = 0.02) and LZAP (r = 0.5, p = 0.01), but not with FVC% (r = 0.4, p = 0.07). Additionally, TST and SE correlated negatively with residual volume% (r = -0.4, p = 0.046, and r = -0.4, p = 0.03, respectively). There was no correlation between TST and SE and measures of nocturnal oxygenation. Multiple linear regression was used to predict TST, with 50% (r(2) = 0.49) explained by a combination of LZAP (27%), mean SaO(2) (23%), and the lowest SaO(2) (< 1%). To predict SE, 44% (r(2) = 0.43) was explained by a combination of LZAP (29%), mean SaO(2) (14%), and the lowest SaO(2) (1%). CONCLUSION: Although parameters of respiratory function and mechanics correlate with sleep quality, both nocturnal oxygenation and measurements of respiratory function/mechanics predict sleep quality in severe emphysema.

Effect of Triple Therapy with Budesonide-Formoterol-Tiotropium Versus Placebo-Tiotropium on Sleep Quality in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Factors responsible for poor sleep quality in patients with chronic obstructive pulmonary disease (COPD) includes the effects of medications. This study evaluates the effect of the inhaled triple therapy of budesonide-formoterol-tiotropium versus placebo-tiotropium on sleep quality in COPD patients. METHODS: Twenty-three patients (11 [48%] males; age 55 [51-60, 48--5] years; body mass index [BMI] 25 [22-30, 18-40] kg/m2; forced expiratory volume in 1 second [FEV1]1.10 [0.80 -1.90, 0.60-2.80] L, 42 [31-62, 24-75] % predicted) were studied. Ten patients were randomized to budesonide-formoterol-tiotropium and 13 patients to placebo-tiotropium. At baseline and after 28 days, patients completed spirometry, polysomnography, an Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), COPD-specific St George's Respiratory Questionnaire (SGRQ-C) and short form 36 (SF 36). RESULTS: After 28 days, there was a significant 29% increase in the bedtime FEV1 in the budesonide-formoterol-tiotropium group (from 0.75 [0.55-1.30, 0.50-2.40] L to 1.00 [0.75-1.55, 0.50-3.00] L, p=0.031), with no change in the placebo-tiotropium group (from 1.20 [0.80-1.50, 0.60-1.90] L to 1.15 [0.75-1.55, 0.50-1.80] L, p=0.91). No significant change was found post treatment in sleep efficiency or total sleep time in both the budesonide-formoterol-tiotropium group (from 78 [72-92, 62-98]% to 88 [77-92, 40-98]%, p=0.70 and 290 [268-358, 252-382] min to 342 [303-358, 157-372] min, p=0.77, respectively) and the placebo-tiotropium group (from 82 [75-88, 46-93]% to 84 [77-87, 62-94]%, p=0.96 and 320 [292-350, 180-378] min to 339 [303-349, 241-366] min, p=0.79, respectively). While there was no significant change in the arousal index in the budesonide-formoterol-tiotropium group (9 [5-16, 0-48] arousals/hour to 14 [9-17, 2-36] arousals/hour, p=0.43), a significant increase was seen in the placebo-tiotropium group (11 [4-13, 3--2] arousals/hour to 17 [11-21, 2-33] arousals/hour, p=0.027). Similarly, there was no change in the ESS in the budesonide-formoterol-tiotropium group (6 [3-8, 0-11] to 6 [5-8, 0-1]), p=0.44), but a marginally significant increase in the placebo-tiotropium group (8 [5-12, 2-18] to 10 [7-13, 5-18], p=0.07), with a significant difference in the ESS 28 days post treatment between the 2 groups (6 [5-8, 0-11] versus 10 [7-13, 5-18], p=0.043). There was no significant change in nocturnal oxygenation, sleep architecture, PSQI, SGRQ-C, or SF 36 in both groups. CONCLUSION: In patients with COPD, inhaled triple therapy with budesonide-formoterol-tiotropium as compared to placebo-tiotropium improves pulmonary function while preserving sleep quality and architecture.

Lymphoid follicle cells in chronic obstructive pulmonary disease overexpress the chemokine receptor CXCR3.

RATIONALE: The mechanisms underlying formation of lung lymphoid follicles (LF) in chronic obstructive pulmonary disease (COPD) are unknown. The chemokine receptor CXCR3 regulates immune responses in secondary lymphoid structures elsewhere in the body and is highly expressed by Th1 lymphocytes in the airway in COPD. Because chemokine receptors control inflammatory cell homing to inflamed tissue, we reasoned that CXCR3 may contribute to LF formation in COPD. OBJECTIVES: We assessed the expression of CXCR3 and its ligands (IP-10/CXCL10, Mig/CXCL9, and ITAC/CXCL11) by LF cells in never-smokers, smokers without COPD, and subjects with COPD. METHODS: CXCR3, IP-10, Mig, and ITAC expression were assessed in lung sections from 46 subjects (never-smokers, smokers without COPD [S], and subjects with COPD in GOLD stages 1-4) by immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: CXCR3-expressing T cells (CD8+ or CD4+) and B cells (CD20+) were topographically distributed at the follicle periphery and center, respectively. The percentage of immunohistochemically identified CXCR3+ cells increased progressively while proceeding from S through GOLD 3-4 (P < 0.01 for GOLD 3-4 vs. S). Moreover, the number of CXCR3+ follicular cells correlated inversely with FEV(1) (r = 0.60). The CXCR3 ligands IP-10 and Mig were expressed by several cell types in and around the follicle, including CD68+ dendritic cells/ macrophages, airway epithelial cells, endothelial cells, and T and B cells. CONCLUSIONS: These results suggest that LF form in the COPD lung by recruitment and/or retention of CXCR3-expressing T and B lymphocytes, which are attracted to the region through production of CXCR3 ligands IP-10 and Mig by lung structural and follicular cells.

Treatment of sleep disordered breathing in congestive heart failure.

In patients with congestive heart failure, sleep disordered breathing occurs commonly and is associated with an increased mortality. In addition to central sleep apnea (Cheyne-Stokes respiration), obstructive sleep apnea is more prevalent in patients with congestive heart failure than in the general population. As a result, a number of treatments have been investigated, with varying results. While many therapies may improve the severity of sleep disordered breathing, only positive pressure ventilation has been shown to improve cardiac function. Newer forms of positive pressure ventilation, such as adaptive servo-ventilation, appear to be even more effective at correcting central sleep apnea. Whether any of these treatments have an effect on transplant-free survival is presently unknown and awaits further study.

HIV-1 Nef promotes cell proliferation and microRNA dysregulation in lung cells.

Non-small cell lung cancer (NSCLC) represents about 85% of all lung cancer cases. Lung cancer is the most frequent non-AIDS-defining malignancies in HIV-infected patients. The mechanism of the increased risk for lung cancer in HIV-1 patients is poorly understood. HIV-1 Nef protein has been suggested to be one of the key players in HIV-related lung disease. In here, we showed the involvement of Nef protein in cell modifications such as fibroblasts (IMR-90) and normal (BEAS-2B) or cancerous (A549) epithelial cells. We demonstrated that Nef protein reprograms initial stages of lung cancer (e.g. changes in the metabolism, improved cell survival and invasion, increase the angiogenesis factor VEGF). Additionally, we showed that Nef is provoking a global decrease of mature miRNA and a decrease of DICER1 and AGO expression in lung cells. MiRNAs play a crucial role in cell signaling and homeostasis, functioning as oncogenes or tumor suppressors, and their dysregulation can contribute to the tumorigenic process. These results showed that HIV-1 Nef protein is directly involved in preventing cell death and contributes to tumor progression.

Use of positional therapy when incorporated into a diagnosis-treatment algorithm for obstructive sleep apnea.

PURPOSE: Positional obstructive sleep apnea (OSA) is prevalent. We hypothesized that by incorporating positional therapy into a diagnosis-treatment algorithm for OSA it would frequently be prescribed as an appropriate first-line therapy. METHODS: Fifty-nine members (45 males, 49±9 yrs, BMI 35.2±5.6 kg/m2) of the Law Enforcement Health Benefits (LEHB), Inc. of Philadelphia with clinically suspected OSA were evaluated. Patients completed an Epworth Sleepiness Scale (ESS) questionnaire and a home sleep test (HST). Patients diagnosed with positional OSA (non-supine apnea-hypopnea index [AHI] < 5 events/hr) were offered positional therapy. A cost comparison to continuous positive airway pressure (CPAP) therapy was performed. RESULTS: Fifty-four (92%) of the patients (43 males, 49±9 yrs, BMI 35.2±5.3 kg/m2) had OSA on their HST (AHI 24.2±20.1 events/hr). Sixteen (30%) patients had positional OSA. Compared to non-positional patients, patients with positional OSA were less heavy (32.4±5.1 vs. 36.4±5.1 kg/m2, respectively [p=0.009]), less sleepy (ESS 8±5 vs. 12±5, respectively [p=0.009]), and had less severe OSA (AHI 10.4±4.3 vs. 30.0±21.3 events/hr, respectively [p<0.001]). Thirteen of the 16 patients with positional OSA agreed to positional therapy and 31 non-positional OSA patients agreed to CPAP therapy. Based on initial costs, incorporating positional therapy ($189.95/device compared to CPAP therapy at $962.49/device) into the treatment algorithm resulted in a 24% cost savings compared to if all the patients were initiated on CPAP therapy. CONCLUSION: With the high prevalence of positional OSA, using a diagnosis-treatment algorithm that incorporates positional therapy allows it to be more frequently considered as a cost effective first-line therapy for OSA.

Advanced emphysema in African-American and white patients: do differences exist?

BACKGROUND: Emphysema is the only smoking-related disease in which white patients have higher prevalence and higher attributable mortality rates than African-American patients. Epidemiologic studies have not addressed, nor explained, the observed racial differences in emphysema. STUDY OBJECTIVES: To determine whether white and African-American patients differ with respect to the magnitude, anatomic distribution, and physiologic impairments of emphysema. PATIENTS: Characteristics of patients with severe and very severe emphysema enrolled in the National Emphysema Treatment Trial were examined and compared. Patient demographics, cardiopulmonary function, quality of life, and severity/distribution of the emphysema by quantitative CT were analyzed. RESULTS: Of the 1,218 patients enrolled in the trial, 42 were African American (3.4%) and 1,156 were white (95%). African Americans were younger (mean age +/- SD, 63 +/- 7 years vs 67 +/- 6 years) and smoked less (26 +/- 14 cigarettes per day vs 32 +/- 14 cigarettes per day) than white patients (p = 0.01). There was no difference between the two racial groups in pulmonary function (FEV1, 27 +/- 6% predicted vs 27 +/- 7% predicted), gas exchange (Pa(O2), 66 +/- 11 mm Hg vs 65 +/- 10 mm Hg), and exercise (33 +/- 14 W vs 36 +/- 21 W), respectively. Quality of life measures were similar between the groups, but African Americans had a lower socioeconomic status, lower education level, and fewer were married. Radiographic analysis of the extent of emphysema in African Americans, who were matched with selected white patients, revealed significantly less emphysema in the former group and different distribution of severe emphysema. CONCLUSIONS: African Americans with emphysema were younger and had a similar degree of lung impairment as the white study population despite smoking less. In a subgroup of matched patients, the severity and distribution of emphysema by quantitative radiographic analysis were different.

Effects of lung volume reduction surgery on sleep quality and nocturnal gas exchange in patients with severe emphysema.

STUDY OBJECTIVES: We hypothesized that associated with improvements in respiratory mechanics, lung volume reduction surgery (LVRS) would result in an improvement in both sleep quality and nocturnal oxygenation in patients with severe emphysema. DESIGN: Prospective randomized controlled trial. SETTING: University hospital. PATIENTS: Sixteen patients (10 men, 63 +/- 6 years [+/- SD]) with severe airflow limitation (FEV(1), 28 +/- 10% predicted) and hyperinflation (total lung capacity, 123 +/- 14% predicted) who were part of the National Emphysema Treatment Trial. INTERVENTIONS AND MEASUREMENTS: Patients completed 6 to 10 weeks of outpatient pulmonary rehabilitation. Spirometry, measurement of lung volumes, arterial blood gas analysis, and polysomnography were performed prior to randomization and again 6 months after therapy. Ten patients underwent LVRS and optimal medical therapy, while 6 patients received optimal medical therapy only. RESULTS: Total sleep time and sleep efficiency improved following LVRS (from 184 +/- 111 to 272 +/- 126 min [p = 0.007], and from 45 +/- 26 to 61 +/- 26% [p = 0.01], respectively), while there was no change with medical therapy alone (236 +/- 75 to 211 +/- 125 min [p = 0.8], and from 60 +/- 18 to 52 +/- 17% [p = 0.5], respectively). The mean and lowest oxygen saturation during the night improved with LVRS (from 90 +/- 7 to 93 +/- 4% [p = 0.05], and from 83 +/- 10 to 86 +/- 10% [p = 0.03], respectively), while no change was noted in the medical therapy group (from 91 +/- 5 to 91 +/- 5 [p = 1.0], and from 84 +/- 5 to 82 +/- 6% [p = 0.3], respectively). There was a correlation between the change in FEV(1) and change in the lowest oxygen saturation during the night (r = 0.6, p = 0.02). In addition, there was an inverse correlation between the change in the lowest oxygen saturation during the night and the change in residual volume (- r = 0.5, p = 0.04) and functional residual capacity (- r = 0.6, p = 0.03). CONCLUSION: In patients with severe emphysema, LVRS, but not continued optimal medical therapy, results in improved sleep quality and nocturnal oxygenation. Improvements in nocturnal oxygenation correlate with improved airflow and a decrease in hyperinflation and air trapping.

Respiratory failure after lung transplantation.

STUDY OBJECTIVES: To characterize patients who acquired postoperative respiratory failure after lung transplantation (LT), and to identify risks associated with postoperative respiratory failure and poor surgical outcome. STUDY DESIGN: Retrospective clinical analysis in a tertiary care transplantation center. METHODS: We reviewed the records of 80 consecutive patients who underwent LT from April 1994 to May 1999, analyzing their records for a number of preoperative and perioperative variables and complications. RESULTS: Forty-four patients (55%) acquired postoperative respiratory failure and had a mortality rate of 45%. No difference was noted between patients with respiratory failure and those without in terms of age (mean +/- SD, 56 +/- 9 years vs 53 +/- 11 years), gender, baseline pretransplant arterial blood gas analysis (PaCO(2), 46 +/- 9 mm Hg vs 44 +/- 10 mm Hg), and cardiopulmonary exercise testing (maximum oxygen uptake, 0.76 +/- 0.44 L/min/m(2) vs 0.82 +/- 0.20 L/min/m(2)). Ischemic reperfusion lung injury (IRLI) [55%] and perioperative cardiovascular/hemorrhagic events (36%) were the major contributors to the development of respiratory failure. Preoperative pulmonary hypertension, right ventricular (RV) dysfunction, ischemic times, and need for bilateral LT and cardiopulmonary bypass (CPB) were higher in patients with respiratory failure (p < 0.05) compared to recipients without respiratory failure. However, the presence of preoperative moderate-to-severe RV dysfunction was the only independent factor (odds ratio, 21.9; 95% confidence interval, 1.6 to 309.0). CONCLUSION: Respiratory failure after LT is common and is associated with high morbidity and mortality. Respiratory failure often occurred in patients with operative technical complications, cardiovascular events, and postoperative IRLI, which were observed most in patients requiring CPB because of RV dysfunction.

The effects of high-flow vs low-flow oxygen on exercise in advanced obstructive airways disease.

STUDY OBJECTIVES: Current options to enhance exercise performance in patients with COPD are limited. This study compared the effects of high flows of humidified oxygen to conventional low-flow oxygen (LFO) delivery at rest and during exercise in patients with COPD. DESIGN: Prospective, nonrandomized, nonblinded study. SETTING: Outpatient exercise laboratory. PATIENTS: Ten patients with COPD, stable with no exacerbation, and advanced airflow obstruction (age, 54 +/- 6 years; FEV(1), 23 +/- 6% predicted [mean +/- SD]). INTERVENTIONS: After a period of rest and baseline recordings, patients were asked to exercise on a cycle ergometer for up to 12 min. Exercising was started on LFO first; after another period of rest, the patients repeated exercising using the high-flow oxygen (HFO) system, set at 20 L/min and matched to deliver the same fraction of inspired oxygen (Fio(2)) as that of LFO delivery. MEASUREMENTS AND RESULTS: Work of breathing and ventilatory parameters (tidal volume, respiratory rate, inspiratory time fraction, rapid shallow breathing index, pressure-time product) were measured and obtained from a pulmonary mechanics monitor. Borg dyspnea scores, pulse oximetry, blood gases, vital signs were also recorded and compared between the two delivery modes. Patients were able to exercise longer on high flows (10.0 +/- 2.4 min vs 8.2 +/- 4.3 min) with less dyspnea, better breathing pattern, and lower arterial pressure compared to LFO delivery. In addition, oxygenation was higher while receiving HFO at rest and exercise despite the matching of Fio(2). CONCLUSION: High flows of humidified oxygen improved exercise performance in patients with COPD and severe oxygen dependency, in part by enhancing oxygenation.

Smoking patterns in African Americans and whites with advanced COPD.

BACKGROUND: The prevalence and mortality associated with COPD increases with age, with higher rates observed in whites than African Americans. Causes and explanations for smoking-related racial differences on the respiratory system have not been determined. OBJECTIVE: To investigate racial differences in smoking patterns and lung function in patients with advanced COPD. DESIGN: Retrospective record review of patients with advanced COPD. SETTING: Outpatient pulmonary clinic in a tertiary-care urban hospital. PATIENTS: One hundred sixty patients with advanced COPD (80 African Americans and 80 whites) referred for either lung volume reduction surgery or transplantation evaluation. DATA COLLECTION: Demographics, smoking profile, pulmonary function testing, arterial blood gases, and exercise stress tests were compared between African-American and white patients. RESULTS: Despite comparable pulmonary function, African Americans were younger at presentation and had lower overall pack-years of smoking than whites (58 +/- 10 years vs 62 +/- 8 years, and 44 +/- 23 pack-years vs 66 +/- 31 pack-years, respectively; p < 0.05 [mean +/- SD]). Additionally, African Americans started smoking later in life than whites (18 +/- 5 years vs 16 +/- 4 years). Similarly, women presented at a younger age and smoked less compared to men (58 +/- 9 years vs 62 +/- 9 years, and 49 +/- 28 pack-years vs 61 +/- 29 pack-years, respectively; p < 0.05), without showing any difference in lung function or exercise performance. CONCLUSION: Among susceptible patients with advanced COPD, African Americans and women seem more prone to the effects of tobacco smoke than their counterparts.

Effects of nasal continuous positive airway pressure on oxygen body stores in patients with Cheyne-Stokes respiration and congestive heart failure.

STUDY OBJECTIVES: The mechanism(s) by which nasal continuous positive airway pressure (CPAP) is effective in the treatment of Cheyne-Stokes respiration (CSR) in patients with congestive heart failure (CHF) remains uncertain, and may involve an increase in total oxygen body stores (dampening), changes in central and peripheral controller gain, and/or improvement in cardiac function. The purpose of this study was to evaluate the effects of nasal CPAP on total oxygen stores, as measured by the rate of fall of arterial oxyhemoglobin saturation (dSaO(2)/dt), to determine if dampening may play a role in the attenuation of CSR in patients with CHF. DESIGN: Prospective controlled trial. SETTING: University hospital. PATIENTS: Nine male patients (mean +/- SD age, 59 +/- 8 years) with CHF and a mean left ventricular ejection fraction (LVEF) of 16 +/- 4%. INTERVENTIONS AND MEASUREMENTS: All patients had known CSR, as identified on a baseline polysomnographic study. Patients then underwent repeat polysomnography while receiving nasal CPAP (9 +/- 0.3 cm H(2)O). The polysomnography consisted of recording of breathing pattern, pulse oximetry, and EEG. dSaO(2)/dt was measured as the slope of a line drawn adjacent to the falling linear portion of the arterial oxygen saturation (SaO(2)) curve associated with a central apnea. All patients underwent echocardiography and right-heart catheterization within 1 month of the study to measure LVEF and cardiac hemodynamics, respectively. RESULTS: There was a significant decrease in the apnea-hypopnea index (AHI) with nasal CPAP, from 44 +/- 27 events per hour at baseline to 15 +/- 24 events per hour with nasal CPAP (p = 0.004). When compared to baseline, dSaO(2)/dt significantly decreased with nasal CPAP from 0.42 +/- 0.15% to 0.20 +/- 0.07%/s (p < 0.001). The postapneic SaO(2), when compared to baseline, significantly increased with nasal CPAP, from 87 +/- 5% to 91 +/- 4% (p < 0.05). The preapneic SaO(2) did not significantly change, from a baseline of 96 +/- 2% to 96 +/- 3% with nasal CPAP (p = 0.8). When compared to baseline, the apnea duration and heart rate did not change with nasal CPAP. While there was a significant correlation noted between baseline postapneic SaO(2) and dSaO(2)/dt (r = 0.8, p = 0.02), no correlation was seen between baseline preapneic SaO(2) and dSaO(2)/dt (r = 0.1, p = 0.7). A significant correlation was noted between baseline dSaO(2)/dt and the AHI (r = 0.7, p = 0.02). With CPAP, there was a significant correlation noted between dSaO(2)/dt and the AHI (R = 0.7, p = 0.04), but no correlation was noted between dSaO(2)/dt and postapneic SaO(2) (R = 0.1, p = 0.8). CONCLUSION: Nasal CPAP significantly decreases dSaO(2)/dt and thus increases total body oxygen stores in patients with CSR and CHF. By increasing oxygen body stores, dampening may be one of the mechanisms responsible for the attenuation of CSR seen with nasal CPAP.

Complications of long-term mechanical ventilation.

Complications of LTMV should be considered in the context of underlying diseases and comorbidities, the trigger for ventilator dependency, and site of care. These factors have an impact on outcome and on the type and severity of complications. In view of the complexity of chronically ill VAIs, complications of mechanical ventilation become the major impediment in achieving the ultimate goal of LTMV, extending life, and improving psychophysiologic function and quality of life. Efforts should not be spared to prevent and aggressively treat these complications while continuing plans to wean and rehabilitate the patient.

Determinants of CPAP Adherence in Hispanics with Obstructive Sleep Apnea.

Purpose. We hypothesized that socioeconomic factors and a language barrier would impact adherence with continuous positive airway pressure (CPAP) among Hispanics with obstructive sleep apnea (OSA). Methods. Patients with OSA who were prescribed CPAP for at least 1 year and completed a questionnaire evaluating demographic data, socioeconomic status, and CPAP knowledge and adherence participated in the study. Results. Seventy-nine patients (26 males; 53 ± 11 yrs; body mass index (BMI) = 45 ± 9 kg/m(2)) with apnea-hypopnea index (AHI) 33 ± 30 events/hr completed the study. Included were 25 Hispanics, 39 African Americans, and 15 Caucasians, with no difference in age, AHI, CPAP use, or BMI between the groups. While there was a difference in educational level (P = 0.006), income level (P < 0.001), and employment status (P = 0.03) between the groups, these did not influence CPAP adherence. Instead, overall improvement in quality of life and health status and perceived benefit from CPAP influenced adherence, both for the group as a whole (P = 0.03, P = 0.004, and P = 0.001, resp.), as well as in Hispanics (P = 0.02, P = 0.02, P = 0.03, resp.). Conclusion. In Hispanic patients with OSA, perceived benefit with therapy, rather than socioeconomic status or a language barrier, appears to be the most important factor in determining CPAP adherence.

Comparison of positional therapy to CPAP in patients with positional obstructive sleep apnea.

STUDY OBJECTIVES: We hypothesized that positional therapy would be equivalent to continuous positive airway pressure (CPAP) at normalizing the apnea-hypopnea index (AHI) in patients with positional obstructive sleep apnea (OSA). METHODS: Thirty-eight patients (25 men, 49 +/- 12 years of age, body mass index 31 +/- 5 kg/m2) with positional OSA (nonsupine AHI <5 events/h) identified on a baseline polysomnogram were studied. Patients were randomly assigned to a night with a positional device (PD) and a night on CPAP (10 +/- 3 cm H2O). RESULTS: Positional therapy was equivalent to CPAP at normalizing the AHI to less than 5 events per hour (92% and 97%, respectively [p = 0.16]). The AHI decreased from a median of 11 events per hour (interquartile range 9-15, range 6-26) to 2 (1-4, 0-8) and 0 events per hour (0-2, 0-7) with the PD and CPAP, respectively; the difference between treatments was significant (p < 0.001). The percentage of total sleep time in the supine position decreased from 40% (23%-67%, 7%-82%) to 0% (0%-0%, 0%-27%) with the PD (p < 0.001) but was unchanged with CPAP (51% [36%-69%, 0%-100%]). The lowest SaO2 increased with the PD and CPAP therapy, from 85% (83%-89%, 76%-93%) to 89% (86%-9%1, 78%-95%) and 89% (87%-91%, 81%-95%), respectively (p < 0.001). The total sleep time was unchanged with the PD, but decreased with CPAP, from 338 (303-374, 159-449) minutes to 334 (287-366, 194-397) and 319 (266-343, 170-386) minutes, respectively (p = 0.02). Sleep efficiency, spontaneous arousal index, and sleep architecture were unchanged with both therapies. CONCLUSION: Positional therapy is equivalent to CPAP at normalizing the AHI in patients with positional OSA, with similar effects on sleep quality and nocturnal oxygenation.

Comorbidities in chronic obstructive pulmonary disease.

Comorbidities such as cardiac disease, diabetes mellitus, hypertension, osteoporosis, and psychological disorders are commonly reported in patients with chronic obstructive pulmonary disease (COPD) but with great variability in reported prevalence. Tobacco smoking is a risk factor for many of these comorbidities as well as for COPD, making it difficult to draw conclusions about the relationship between COPD and these comorbidities. However, recent large epidemiologic studies have confirmed the independent detrimental effects of these comorbidities on patients with COPD. On the other hand, many of these comorbidities are now considered to be part of the commonly prevalent nonpulmonary sequelae of COPD that are relevant not only to the understanding of the real burden of COPD but also to the development of effective management strategies.

Mortality and functional performance in severe emphysema after lung volume reduction or transplant.

The purpose of this endeavor is to compare the morbidity, mortality and costs of LVRS versus transplantation in severe emphysema. This was a retrospective review of severe emphysema patients who received LVRS (n = 70) from 1994-1999, or transplant (n = 87) from 1994-2004. Change in functional status was calculated by the change in modified BODE (mBODE) score. Financial data included physician, hospital and medication costs. Preoperatively, there was no significant difference between the transplant and LVRS groups (mean +/- SD) in age (57.7 +/- 5.7 vs. 59.1 +/- 8.3 years), BMI, Borg dyspnea score, 6-minute walk distance or mBODE (10.4 +/- 2.6 vs. 9.6 +/- 2.7, p = 0.4). Preoperatively, FEV1% (23.6 +/- 8.5 vs. 31.9 +/- 17.7, p = 0.008) was significantly lower in the transplant group. One year post-operatively, transplantation patients had a significantly greater improvement in mBODE (-5.7 vs. -2.0, p = 0.0004), FEV1% (43.4 vs. 2.2%, p = 0.0004) and Borg score (-3.0 vs. -1.4, p = 0.04). Transplantation patients had lower long-term survival compared to LVRS patients (p = 0.01). The only variable that affected survival was type of surgery favoring LVRS (hazard ratio 1.7, 95% confidence limits 1.05-2.77). During a mean follow-up of 2.4 +/- 2.5 years after transplant and 5.0 +/- 3.1 years after LVRS, transplantation mean total costs were greater ($381,732 vs. $140,637, p < 0.0001). Transplantation patients spent more time in the hospital (74.3 +/- 81.3 vs. 39.5 +/- 66.7 days, p = 0.009) and had more outpatient visits (29.9 +/- 28.8 vs. 12.3 +/- 12.6 visits, p < 0.0001). In patients who survive over 1 year, transplantation provides a higher level of functional status and a greater improvement in airflow obstruction, dyspnea, exercise tolerance, and mBODE score, but costs more and carries greater mortality.

Effects of oxygen therapy on left ventricular function in patients with Cheyne-Stokes respiration and congestive heart failure.

STUDY OBJECTIVES: Whereas both oxygen therapy and nasal continuous positive airway pressure (CPAP) decrease the apnea-hypopnea index (AHI) in patients with Cheyne-Stokes respiration (CSR) and congestive heart failure (CHF), only nasal CPAP is known to affect the left ventricular ejection fraction (LVEF). We therefore evaluated the effects of 1 month of nocturnal oxygen therapy on LVEF. METHODS: Ten patients (52 +/- 12 years) with CHF (LVEF of 12% +/- 5%) and CSR (AHI 57 +/- 61 events/hour) were studied. Polysomnograms identified CSR and were repeated on oxygen initially (oxygen night 1 [2 L/min]) and after 30 nights (oxygen night 2). LVEF was measured by radionuclide ventriculography. RESULTS: Oxygen therapy decreased the AHI from a baseline of 57 +/- 61 to 9 +/- 11 and 12 +/- 17 events per hour during oxygen nights 1 and 2, respectively (p < .05), with no difference between treatment nights. The lowest oxygen saturation increased during oxygen nights 1 and 2, from a baseline of 87% +/- 7% to 94% +/- 4% and 91% +/- 7%, respectively (p < .05), with no difference between treatment nights. The LVEF did not significantly change from a baseline of 22% +/- 11% to 19% +/- 9% after 1 month of nocturnal oxygen (p = .05). Compared to baseline, there was no change in circulation time during oxygen nights 1 and 2, from 24 +/- 8 seconds to 30 +/- 15 seconds and 23 +/- 6 seconds, respectively (p = .2). Total sleep time, sleep efficiency, and sleep architecture, when compared with baseline, remained unchanged during both oxygen therapy nights. CONCLUSIONS: Although 1 month of nocturnal oxygen therapy decreases the AHI in patients with CSR and CHF, there is no improvement in left ventricular function.