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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/m(2); forced expiratory volume in 1 second [FEV(1)]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 FEV(1) 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 [7­13, 5­18], 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.

Introduction Use of high flow nasal therapy (HFNT) to treat COVID-19 pneumonia has been greatly debated around the world due to concern for increased healthcare worker transmission and delays in invasive mechanical Ventilation (IMV). Herein we analyze the utility of the ROX index to predict the need and timing for IMV in a retrospective analysis of patients with COVID-19 with moderate to severe hypoxemic respiratory failure treated with HFNT. Methods This was a retrospective analysis of 129 consecutive patients with COVID-19 admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to May 17, 2020 with moderate to severe hypoxemic respiratory failure treated with High Flow nasal therapy (HFNT). HFNT patients were divided into two groups: HFNT only and HFNT progressed to IMV. The primary outcome was the ability of the ROX index to predict the need of IMV. Secondary outcomes were mortality, rates of intubation, length of stay (LOS) and rates of nosocomial infections in our cohort treated with HFNT were also reported. Results 837 patients with COVID-19 were screened, 129 met inclusion criteria. The mean age was 60.8(+13.6) years, BMI 32.6(+8), 58(45 %) were female, 72(55.8%) were African American, 40 (31%) Hispanic. 48 (37.2%) were smokers. Of the 129, 89 were HFNT only group whereas 40 in the HFNT progressed to IMV group. Mean time to intubation was 2.5 days(+ 3.3). The 89 HFNT only patients had a significant improvement in ROX from initiation of HFNT at all recorded time points. In contrast, the ROX in HFNT progressed to IMV patients remained unchanged or decreased over time. ROX index of less than 5 at HFNT initiation was predictive of progression to IMV (OR = 2.137, p = 0,052). Any decrease in ROX index after HFNT initiation was predictive of intubation (OR= 14.67, p 0), peak D-dimer >4000 and admission GFR < 60 ml/min were very strongly predictive of need for IMV (ROC = 0.86, p=0.001). Mortality was 11.2% in HFNT only group versus 47.5% in the HFNT progressed to IMV group (p = 0.0001). Mortality and need for pulmonary vasodilators were higher in the HNFT progressed to IMV group. Conclusion ROX index is a valuable, noninvasive tool to evaluate patients with moderate to severe hypoxemic respiratory failure in COVID-19 treated with HFNT. ROX helps predicts need for IMV and thus limiting morbidity and mortality associated with IMV.

BackgroundPulmonary hypertension (PH) causes increased morbidity and mortality in patients with interstitial lung diseases (ILD). Classification schemes, while well-characterised for the vasculopathy of idiopathic PH, have been applied, unchallenged, to ILD-related PH. We evaluated pulmonary arterial histopathology in explanted human lung tissue from patients who were transplanted for advanced fibrotic ILD.MethodsLung explants from 38 adult patients who underwent lung transplantation were included. Patients were divided into three groups: none, mild/moderate and severe PH by mean pulmonary artery pressure (mPAP) measured at pre lung transplantation right heart catheterisation (RHC). Grading of pulmonary vasculopathy according to Heath and Edwards scheme, and prelung transplantation evaluation data were compared between the groups.Results38 patients with fibrotic ILDs were included, the majority (21) with idiopathic pulmonary fibrosis. Of the 38 patients, 18 had severe PH, 13 had mild/moderate PH and 7 had no PH by RHC. 16 of 38 patients had severe pulmonary arterial vasculopathy including vascular occlusion with intimal fibrosis and/or plexiform lesions. There were no correlations between mPAP and lung diffusion with the severity of pulmonary arterial pathological grade (Spearman’s rho=0.14, p=0.34, rho=0.11, p=0.49, respectively).ConclusionsPatients with end stage ILD had severe pulmonary arterial vasculopathy in their explanted lungs irrespective of the presence and/or severity of PH as measured by RHC. These findings suggest that advanced pulmonary arterial vasculopathy is common in patients with advanced fibrotic ILD and may develop prior to the clinical detection of PH by RHC.

Background The use of high-flow nasal therapy (HFNT) to treat COVID-19 pneumonia has been greatly debated around the world due to concerns about increased health care worker transmission and delays in invasive mechanical ventilation (IMV). Herein, we analyzed the utility of the noninvasive ROX (ratio of oxygen saturation) index to predict the need for and timing of IMV. Objective This study aimed to assess whether the ROX index can be a useful score to predict intubation and IMV in patients receiving HFNT as treatment for COVID-19–related hypoxemic respiratory failure. Methods This is a retrospective cohort analysis of 129 consecutive patients with COVID-19 admitted to Temple University Hospital in Philadelphia, PA, from March 10, 2020, to May 17, 2020. This is a single-center study conducted in designated COVID-19 units (intensive care unit and other wards) at Temple University Hospital. Patients with moderate and severe hypoxemic respiratory failure treated with HFNT were included in the study. HFNT patients were divided into two groups: HFNT only and intubation (ie, patients who progressed from HFNT to IMV). The primary outcome was the value of the ROX index in predicting the need for IMV. Secondary outcomes were mortality, rate of intubation, length of stay, and rate of nosocomial infections in a cohort treated initially with HFNT. Results Of the 837 patients with COVID-19, 129 met the inclusion criteria. The mean age was 60.8 (SD 13.6) years, mean BMI was 32.6 (SD 8) kg/m², 58 (45%) were female, 72 (55.8%) were African American, 40 (31%) were Hispanic, and 48 (37.2%) were nonsmokers. The mean time to intubation was 2.5 (SD 3.3) days. An ROX index value of less than 5 at HFNT initiation was suggestive of progression to IMV (odds ratio [OR] 2.137, P=.052). Any further decrease in ROX index value after HFNT initiation was predictive of intubation (OR 14.67, P Conclusions The ROX index helps decide which patients need IMV and may limit eventual morbidity and mortality associated with the progression to IMV.

Introduction Approximately 30% of patient with obstructive sleep apnea (OSA) have positional OSA [non-supine apnea-hypopnea index (AHI) < 5 events/hr]. However, the prevalence is based on variable definitions for hypopneas related to the degree of oxygen desaturation. In addition, use of a home sleep apnea test (HSAT) to identify positional OSA is limited. We hypothesized that in patients evaluated with an HSAT, using a definition for hypopneas based on 4% compared to 3% oxygen desaturation will significantly decrease the percentage diagnosed with positional OSA. Methods Fourteen patients with positional OSA based on a non-supine respiratory event index (REI) < 5 events/hr were included. The initial diagnosis was determined based on a hypopnea definition of ≥ 3% oxygen desaturation. The studies were reanalyzed using a hypopnea definition of ≥ 4% oxygen desaturation. Results Fourteen patients [9 (64%) males, 46±14 yrs, BMI 31±6 kg/m2, ESS 7±5, REI 9±3 events/hr, mean SaO2 94±2%, lowest SaO2 81±6%, %TST SaO2 < 90% 4±6%] were identified with positional OSA (supine REI 16±7 events/hr, non-supine REI 3±1 events/hr) using a hypopneas definition of ≥ 3% oxygen desaturation. When reanalyzed using a hypopnea ≥ 4% oxygen desaturation there was a significant decrease in the REI to 7±2 events/hr (p Conclusion In patients with mild positional OSA, using a hypopnea definition of at least 4% vs. 3% oxygen desaturation on a HSAT will have a significant effect on the overall REI and often exclude patients who would otherwise be treated for OSA. Support None.

Introduction Recently, the measurement of the hypoxic burden and apnea-hypopnea duration has been shown to correlate with mortality in patients with obstructive sleep apnea (OSA). We hypothesized that in patients with mild positional OSA (apnea-hypopnea index [AHI] < 5 events/hr in the non-supine position) the hypoxic burden would be increased and apnea-hypopnea duration shortened and similar to patients with non-positional OSA. Methods Fourteen patients with positional OSA and 24 patients non-positional OSA with similar severity of OSA based on the respiratory event index (REI) were included. All patients had a home sleep apnea test for suspected OSA. The hypoxic burden was calculated by the multiplication of REI and the mean area under the desaturation curves. Results Thirty-eight patients [12 (35%) males, 50±12 yrs, BMI 35±7 kg/m2, Epworth Sleepiness Scale (ESS) 11±8, REI 10±3 events/hr, apnea-hypopnea duration 19±4 sec, mean SaO2 94±2%, lowest SaO2 79±8%, % total sleep time (TST) SaO2 < 90% 11±16%, hypoxic burden 30±17 %min/hr] completed the study. Fourteen patients [9 (64%) males, 46±14 yrs, BMI 31±6 kg/m2, ESS 7±5, REI 9±3 events/hr, mean SaO2 94±2%, lowest SaO2 81±6%, %TST SaO2 < 90% 4±6%] had positional OSA (supine REI 16±7 events/hr, non-supine REI 3±1 events/hr) and 24 patients had non-positional OSA [3 (13%) males, 52±10 yrs, BMI 38±7 kg/m2, ESS 12±9, REI 10±3 events/hr, mean SaO2 94±2%, lowest SaO2 77±9%, %TST SaO2 < 90% 14±19%]. The hypoxic burden was elevated in both the positional and non-positional OSA patients with no difference between the groups (26±19 %min/hr and 32±15 %min/hr, respectively, p=0.13). The apnea-hypopnea duration was similar in positional and non-positional OSA patients (20±3 sec and 18±4 sec, respectively, p=0.08 sec). Conclusion In patients with mild positional OSA the hypoxic burden, which has been associated with cardiovascular mortality, is elevated and similar to patients with non-positional OSA. Support None

Contains fulltext : 220761.pdf (Publisher’s version ) (Open Access) Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue-->Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway-->Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P < 0.001] in the Tissue-->Airway group; r = -0.14 [P = 0.011] in the Airway-->Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."

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

Pulmonary hypertension is a serious complication of sarcoidosis. This review discusses clinical characteristics of patients with sarcoid-associated pulmonary hypertension (SAPH) and pitfalls in the diagnosis, and highlights potential therapies.SAPH is common in patients with advanced disease, but it can occur in patients with minimal disease burden. Risk factors for SAPH include restrictive lung physiology, hypoxemia, advanced Scadding chest X-ray stage, and low carbon monoxide diffusion capacity. Echocardiogram is a good initial screening tool in the diagnosis of pulmonary hypertension, but right heart catheterization is necessary to confirm the diagnosis. Treatment with pulmonary vasodilators, including endothelin antagonists, can lead to improvements in pulmonary hemodynamics in some patients but may not improve their exercise capacity. Forced vital capacity is an important predictor of exercise performance in patients with SAPH. Clinical observations and response to specific therapies for pulmonary hypertension suggest the presence of different SAPH phenotypes.Patients who complain of persistent dyspnea should be screened for the presence of pulmonary hypertension. The prognosis of SAPH is poor and it is prudent to consider referral of these patients for lung transplantation. In some patients with SAPH, treatment with anti-inflammatory agents and pulmonary vasodilators can lower pulmonary arterial pressures, improve dyspnea and functionality, and enhance overall quality of life.

The presence of obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD) is referred to as the OSA-COPD overlap syndrome. While lung inflation has been shown to be an important factor in determining upper airway stability, its role in determining OSA severity in smokers, including those with emphysema, has not been evaluated.To evaluate the importance of lung inflation on OSA severity (apnea-hypopnea index [AHI]) in smokers with suspected OSA.Fifty-one smokers (18 males; mean [±SD] age, 59 ± 9 yr; body mass index [BMI], 32 ± 9 kg/m(2)) who were part of the Genetic Epidemiology of COPD (COPDGene) project were studied. Patients underwent a full-night polysomnography for suspected OSA. Other testing included spirometry and volumetric chest computed tomography (CT) for quantitative measurement of CT-derived percent emphysema and CT-derived percent gas trapping.For the group overall, there was evidence of obstructive airway disease by spirometry (FEV1, 1.4 ± 0.5 L, 58 ± 14% predicted) and emphysema by quantitative CT (CT-derived percent emphysema, 11 ± 13%; CT-derived percent gas trapping, 31.6 ± 24.1%). Twenty-nine (57%) of the patients had OSA (AHI, 18 ± 12 events/h). Patients with OSA had a higher BMI but were younger than those without OSA (BMI, 35 ± 9 kg/m(2) vs. 29 ± 7 kg/m(2), respectively [P = 0.007]; age, 56 ± 8 yr vs. 62 ± 9 yr, respectively [P = 0.01]). There was an inverse correlation between the AHI and the CT-derived percent emphysema and CT-derived percent gas trapping, both for the entire group (r = -0.41 [P 0.01] and r = -0.44 [P 0.01], respectively) and when just those patients with OSA were evaluated (r = -0.43 [P = 0.04] and r = -0.49 [P = 0.03], respectively). Multiple linear regression revealed that, in addition to CT-derived percent emphysema and CT-derived percent gas trapping, sex and BMI were important in determining the AHI in these patients.In smokers with OSA, increased gas trapping and emphysema as assessed by CT are associated with a decreased AHI. Along with sex and BMI, these measurements may be important in determining the severity of OSA in patients with COPD and may offer a protective mechanism in patients with more advanced disease.

Background CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

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.

Background One of the main stimuli that cause asthma exacerbations in children is physical activity, and exercise-induced bronchospasm (EIB) occurs in most asthmatic patients. Objective To investigate the level of preparedness for a potential EIB event in suburban children involved in recreational sports. Methods A cross-sectional study, focusing on children 12 years and younger, who participated in Little League baseball or soccer in Lower Merion Township, PA, was conducted by clinical survey. The survey was performed during a face-to-face encounter with the parent or caretaker of the child. Results Five hundred seventy-nine children 12 years and younger were surveyed. The parents or caretakers of 80 reported a history of asthma, indicating a prevalence of 14%. Only 18 (22%) of these children with asthma were reported to have a rescue medicine readily available. The 95% confidence interval was 14.22% to 33.47%, indicating that we can be 95% certain that the true population with rescue medication lies between 14% and 33%. Conclusions Despite having been diagnosed as having asthma, more than 75% of children surveyed were unprepared for an EIB event. Measures should be explored to improve the quality of care of asthmatic children involved in community sports. We also propose that it may be beneficial for first-aid kits to include a β 2 -agonist bronchodilator.

Approximately 85% of all cases of chronic obstructive pulmonary disease are attributed to cigarette smoking. The only other established risk factor for the development of chronic obstructive pulmonary disease that is of comparable importance is the deficiency of alpha1‐antitrypsin, a rare genetic defect that is present in less than 1% of all cases. Other risk factors are not well characterized in the literature. This article describes one patient without a significant smoking history and a normal alpha1‐antitrypsin level that developed severe early‐onset emphysema and gives a brief discussion about other genetic and environmental risk factors for the development of emphysema.

Background It is believed that there are many high school-age athletes who have undiagnosed asthma or exercise-induced asthma (EIA). The screening of these athletes for EIA will allow them to be identified and treated. Objectives 1) To obtain reliable peak expiratory flow rate (PEFR) measurements and administer questionnaires to high school-age athletes to evaluate their asthma risk. 2) To identify high-risk athletes for having EIA or asthma by a free run challenge test. 3) To evaluate whether an athlete's present asthma control is adequate. 4) To evaluate these tools for their value as screening tools for asthma or EIA. Methods Eight hundred one student athletes from 10 suburban Pittsburgh schools were screened for more than 18 months for asthma as part of their preparticipation sports physicals. The screening included all athletes from all high school sports. The athletes were given a brief questionnaire, had PEFR measured, and then participated in a free running exercise challenge. Results Forty-six of 801 athletes had asthma or EIA, Of the remaining 755 athletes, 49 athletes were identified as having undiagnosed asthma. In the previously unrecognized athletes with EIA, the positive and negative predictive value of the questionnaire was 42% and 97%, respectively. Eighty-five percent (39 of 46) of the known asthmatic athletes, using their recommended medication, failed their free running test by a >15% drop of their PEFR. Conclusions The free running test is a good test for identifying and assessing the athlete with EIA. The PEFR meter is not a good screening tool for EIA in the high school athlete. A questionnaire may be a good negative screening tool, but further development is needed before it can be used for widespread screening.

Published asthma consensus reports now acknowledge that asthma is a nocturnal disease in as many as 75% of those afflicted by this medical condition. Nonetheless, the treatment of this chronic obstructive pulmonary disease in the clinic continues to be based primarily on homeostatic considerations in that it relies on long-acting bronchodilator and other therapies formulated and scheduled to ensure constant or near-constant levels of medication during the 24h. The need of asthma patients prone to nighttime attacks is not the same during the day and night; the therapeutic requirements of patients who experience nocturnal asthma, especially ones with the more severe forms of the disease, are often not satisfied by conventional medications. The therapeutic response and patient tolerance to bronchodilator medications can be improved markedly when the medications are proportioned during the 24h as a chronotherapy, that is, when more medication is delivered during nighttime sleep than daytime activity, as verified by numerous studies. This article reviews how the body's circadian rhythms influence the pharmacokinetics and effects of commonly prescribed asthma therapies and addresses why and how they must be taken into consideration to increase the effectiveness of asthma treatment.

Background Exercise-induced bronchospasm (EIB) affects up to 35% of athletes and up to 90% of asthmatics. Asthma morbidity and mortality have increased over the past several decades among residents of Philadelphia, PA. It is possible that a simple free running test for EIB may serve as a tool to study the factors contributing to recent trends in asthma, and to screen for asthma in athletes in the urban setting. Objectives The purposes of this study were to (1) assess a free running test to screen for EIB, and (2) examine prevalence of and epidemiologic factors associated with EIB in high school athletes. Design Cross-sectional observational study on the incidence and risk factors for EIB. To validate our method and criteria for the diagnosis of EIB, a repeat test was performed on a portion of the athletes. In a randomized single-blinded fashion, 15 athletes who had demonstrated EIB initially received albuterol or placebo prior to a repeat exercise test. Setting Community high school athletic facilities. Participants We studied 238 male high school varsity football players. Intervention All athletes underwent an acquaintance session with a questionnaire, followed by a 1-mile outdoor run (6 to 8 mins). Measurements Peak expiratory flow (PEF) measurements were determined prior to and 5, 15, and 30 min after exercise. Heart rates (HRs) and dyspnea scores were measured. EIB was defined as a decrease of 15% in PEF at any time point after exercise. Associations of EIB with demographic factors were assessed by univariate and multivariate analyses. Results Two hundred thirty-eight athletes participated: 92 European-Americans (EA), 140 African-Americans (AA), 5 Hispanics, and 1 Native American. Mean age was 16 ± 1 years. Average HR postexercise was 156 ± 24 beats/min. Twenty-four (10%) reported a history of treated asthma. The prevalence of EIB among the remaining 214 athletes was 19 of 214 (9%). The rate of EIB among AA athletes was higher than among EA athletes: (17/126 [13%] AA vs 2/82 [2%] EA, p = 0.01). During the validation portion of the study, the placebo-treated group (n = 7) demonstrated a consistent drop in PEF after exercise on repeat testing, with a 16 ± 5% fall in PEF on initial testing and a 14 ± 13 drop with placebo. In contrast, the fall in airflow in the albuterol-treated athletes (n = 8) following exercise reversed with albuterol treatment, from a 15 ± 6% fall in PEF at initial testing to an increase in PEF of 6 ± 9% from baseline following albuterol administration. A history of wheezing (p Conclusions Our findings indicate a substantial rate of unrecognized EIB exists among urban varsity athletes, and suggest that active screening for EIB, especially for students residing in poverty areas, may be indicated to identify individuals at risk for EIB and asthma.

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/m2) with apnea-hypopnea index (AHI)33±30events/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, andP=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.

Asthma is an inflammatory disease involving the airways. E-series prostaglandins have potent anti-inflammatory effects on neutrophils and T lymphocytes. Accordingly, we tested the acute (i.e., 6 h) and chronic (i.e., 1 week) effects of oral misoprostol 200 mg in five stable asthmatics. A double-blind, randomized, crossover design was used. Airway function was assessed from measurements of forced expiratory volume in 1 s (FEV(1)). The number of puffs of the inhaled beta-adrenergic agonist bronchodilator, albuterol, taken for symptomatic rescue, was assessed by diary. FEV(1) measured serially for 6 h after 200 mg misoprostol was similar on misoprostol and placebo days in all subjects. In contrast, three of the five subjects showed appreciable increases in FEV(1) during a week of misoprostol compared to either baseline or placebo week. Two subjects showed no change in the FEV(1) with 1 week of misoprostol. All three of the subjects who kept a diary decreased the number of puffs of albuterol during the misoprostol compared to placebo period. Of note, in these three subjects, airway function improved (n = 1) or remained the same (n = 2) despite a diminution in the number of puffs of a beta-agonist administered. None of the subjects administered the 200-mg oral dose QID reported any significant symptoms or adverse reaction. In conclusion, several inferences can be drawn from this early preliminary study. These data suggest that a trial involving a large number of subjects, a longer period of treatment, and a more objective method of assessing inhaler use may be useful in evaluating the chronic effects of misoprostol in asthma.

The most critically ill patients in the hospital are located in the ICU. Due to intensive individualized care and monitoring, these patients often suffer from severe sleep deprivation. The amount and continuity of sleep as well as normal sleep architecture are all affected. Moreover, by impairing protein synthesis, cell division, and cellular immunity, sleep deprivation can affect the healing process and thus contribute to an increased morbidity and mortality. Reasons for sleep deprivation appear to be multifactorial and include the following: the patient's chronic underlying illness, an acute superimposed illness or surgical procedure, medications used in treatment of the primary illness, and the ICU environment itself. Therapeutic interventions need to address each of these potential causes, with an emphasis placed on providing an environment that is both diurnal and focused on the importance of uninterrupted sleep.

Once-daily morning (7 AM) vs evening (10 PM) administration of the terbutaline prodrug bambuterol (20-mg tablet dose) was investigated in a double-blind, cross-over, randomized, and placebo-controlled study involving 29 diurnally active patients with asthma. Terbutaline plasma concentration, spirometry, and drug tolerance were assessed during 39-h inpatient studies. A 7-day washout period separated each treatment. Mean 24-h plasma concentration was comparable for morning and evening bambuterol (13.2 vs 14.0 nmol/L). The Cmax for evening vs morning dosing was 17.2 vs 15.5 nmol/L (p < 0.02). The 24-h mean FEV1 was greater (p < 0.001) for bambuterol (morning: 3.2 L; evening: 3.4 L) vs placebo (2.9 L) as it was for FVC, FEF25-75%, and peak expiratory flow rate (PEFR), with the maximum effect at 4 AM independent of medication time. Evening dosing, however, resulted in greatest 7 AM (awakening) FEV1, FEV25-75, and PEFR (p < 0.03). With reference to corresponding-in-time placebo values, improvement in FEV1 at the end of the 24-h dosing intervals amounted to 0.34 L (13.5%) (p < 0.0004) and 0.35 L (15.9%) (p < 0.0012) with evening and morning bambuterol dosing, respectively. Side effects were greater for bambuterol than placebo, but not significantly so. Once-daily bambuterol therapy proved to be an effective treatment for asthma, whether administered in the evening or morning. Evening dosing seems best for nocturnal asthma since airway patency overnight and on awakening at 7 AM is most improved.

Without proper treatment, the mortality of pulmonary mucormycosis is nearly 100%. Although the diagnosis is often made histologically, it can be suspected when patients have a reverse halo sign on computed tomography (CT) of the chest, along with the right clinical findings. We describe the case of a woman 7 months post renal transplant who presented with fevers, malaise, and chest pain. Her chest CT revealed a round, focal area of ground-glass attenuation surrounded by a complete rim of consolidation in the left upper lobe, consistent with the reverse halo sign. Pulmonary mucormycosis was diagnosed by transbronchial lung biopsy. She was successfully treated with combined medical and surgical therapies. In the context of this case, we provide a brief review of the diagnosis of pulmonary mucormycosis, with a focus on radiographic and pathologic findings.

Granulomatosis with Polyangiitis (GPA), formerly known as Wegener’s Granulomatosis, is a multisystem disease that predominantly involves the respiratory tract and the kidneys. The pathological hallmarks are necrotizing granulomatous lesions and vasculitis of small and/or medium vessels. It is difficult to diagnose because its presentation is similar to many common diseases such as upper respiratory tract infections, pneumonia, and asthma. Understanding the signs and symptoms, laboratory findings, and biopsy results are key to making the diagnosis of Granulomatosis with Polyangiitis. A heightened degree of clinical suspicion for this rare disease will often lead to the correct diagnosis.

This is the fifth and final article in a continuing education series on chronobiology. Previous articles have provided an overview of chronobiology’s general principles, and its relation to the endocrine system, melatonin, and myocardial infarction. This article discusses how pharmacologic therapy can be optimized by applying principles of chronobiology. Drug absorption and excretion are influenced by circadian rhythms. Teak drug levels can be timed to coincide with the biologic rhythm of symptoms, and drug-level troughs can be scheduled to match the times the body is most sensitive to adverse drug effects. The treatment of asthma and allergic rhinitis and the use of tumor chemotherapeutic agents illustrate how chronopharmacology is applied in practice.

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.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.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%).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.

Chronobiology is the study of biologic rhythms and biologic time structure. Medical chronobiology, in particular, is concerned with circadian (24-h) and other bioperiodic influences on human diseases such as (1) their occurrence or variation in severity over the 24-h or other time scale, (2) response of patients to diagnostic procedures and tests and, (3) the effect of medical treatments. The symptoms of chronic diseases--allergic rhinitis, regular and variant type angina, rheumatoid and osteoarthritis, asthma, epilepsy, hypertension and ulcer disease, for example, commonly exhibit circadian, menstrual cycle (in women), and seasonal patterns. The life-threatening events of myocardial and cerebral infarction and cerebral hemorrhage also exhibit predictable-in-time patterns over 24 h and the year. In the clinic, bioperiodicities strongly influence the results of blood pressure assessment, cutaneous antigen testing and spirometric evaluation, to mention but a few. Bodily rhythms also affect the pharmacokinetics and dynamics of medications. A major goal of medical chronobiology is chronotherapeutics, the optimization of pharmacotherapies, taking into consideration rhythm-dependencies in the kinetics and dynamics of medications plus predictable-in-time variability in the manifestation and severity of human disease. The concepts of medical chronobiology are discussed in detail herein. Examples have been chosen for their relevance to clinical allergy and chest medicine.

Critical care study guide : , Critical care study guide : , کتابخانه دیجیتال جندی شاپور اهواز

After studying this chapter, you should be able to: Recognize the signs and symptoms of selected neurologic conditions, and the approach to diagnosis. Discuss treatments used in selected neurologic conditions. Appreciate the diverse array of neurologic diseases that may be encountered in the intensive care unit. Recognize ethical aspects of selected neurologic disorders.

Define massive pulmonary embolism (MPE). Understand the hemodynamic and pulmonary gas exchange abnormalities associated with MPE. Recognize the different treatment options available for patients with MPE.

Identify risk factors associated with the development of deep vein thrombosis and its consequence, pulmonary embolism. Understand the indications and contraindications for medical, mechanical, and inferior vena cava filter prophylaxis, and describe the available methods for each. Identify the major physiologic mechanism associated with stress-induced gastritis and ulceration, and identify the risk factors associated with this condition. Know the methods used for prophylaxis of stress-induced gastritis and ulceration and the potential complications of the medical therapies used for this condition. Identify the nosocomial infections common in the intensive care unit and the causative organisms responsible. Discuss the various risk factors associated with the development of iatrogenic or preventable infection in critically ill patients. Employ a variety of effective prophylactic regimens to nosocomial infection in the intensive care unit: healthcare/ventilator associated pneumonia (VAP), catheter-related bloodstream infection, and genitourinary tract infection in critically ill patients.

Heart failure is a highly prevalent condition, particularly among elderly adults and women. In diastolic heart failure-or heart failure with normal ejection fraction-left ventricular systolic function is preserved. Although diastolic heart failure is clinically and radiographically indistinguishable from systolic heart failure, echocardiography can reveal a preserved ejection fraction with abnormal diastolic function. The present article reviews current medical concepts related to diastolic heart failure for medical practitioners, particularly primary care physicians, who play a vital role in the care of patients with heart failure. Treatment options, focusing on calcium channel blockers and angiotensin receptor blockers, are discussed. With early diagnosis and proper management, the prognosis of diastolic heart failure can be more favorable than that of systolic heart failure.