Showing papers in "American Journal of Respiratory and Critical Care Medicine in 2005"
TL;DR: Physical activities and movement intensity in patients with chronic obstructive pulmonary disease are assessed with the DynaPort activity monitor and functional exercise capacity is the strongest correlate of physical activities in daily life.
Abstract: Quantification of physical activities in daily life in patients with chronic obstructive pulmonary disease has increasing clinical interest.However,detailedcomparisonwithhealthysubjectsisnotavailable.Furthermore,itisunknownwhethertimespentactivelyduring daily life is related to lung function, muscle force, or maximal and functional exercise capacity. We assessed physical activities and movement intensity with the DynaPort activity monitor in 50 patients (age 64 7 years; FEV1 43 18% predicted) and 25 healthy elderly individuals (age 66 5 years). Patients showed lower walking time (44 26 vs. 81 26 minutes/day), standing time (191 99 vs. 295 109 minutes/day), and movement intensity during walking (1.8 0.3 vs. 2.4 0.5 m/second 2 ;p 0.0001 for all), as well as higher sitting time (374 139 vs. 306 108 minutes/day; p 0.04) and lying time (87 97 vs. 29 33 minutes/day; p 0.004). Walking time was highly correlated with the 6-minute walking test (r 0.76, p 0.0001) and more modestly to maximal exercise capacity, lung function, and muscle force (0.28 r 0.64, p 0.05). Patients with chronic obstructive pulmonary disease are
1,185 citations
TL;DR: Post-traumatic stress reaction consistent with a high risk of PTSD is common in family members of ICU patients and is the rule among those who share in end-of-life decisions.
Abstract: Rationale: Intensive care unit (ICU) admission of a relative is a stressful event that may cause symptoms of post-traumatic stress disorder (PTSD). Objectives: Factors associated with these symptoms need to be identified. Methods: For patients admitted to 21 ICUs between March and November 2003, we studied the family member with the main potential decision-making role. Measurements: Ninety days after ICU discharge or death, family members completed the Impact of Event Scale (which evaluates the severity of post-traumatic stress reactions), Hospital Anxiety and Depression Scale, and 36-item Short-Form General Health Survey during a telephone interview. Linear regression was used to identify factors associated with the risk of post-traumatic stress symptoms. Main results: Interviews were obtained for family members of 284 (62%) of the 459 eligible patients. Post-traumatic stress symptoms consistent with a moderate to major risk of PTSD were found in 94 (33.1%) family members. Higher rates were noted among f...
1,178 citations
TL;DR: The prediction rule is based on 11 simple patient characteristics that were independently associated with mortality and stratifies patients with pulmonary embolism into five severity classes, with 30-day mortality rates of 0-1.6%.
Abstract: Rationale: An objective and simple prognostic model for patients with pulmonary embolism could be helpful in guiding initial intensity of treatment.Objectives: To develop a clinical prediction rule that accurately classifies patients with pulmonary embolism into categories of increasing risk of mortality and other adverse medical outcomes.Methods: We randomly allocated 15,531 inpatient discharges with pulmonary embolism from 186 Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples. We derived our prediction rule using logistic regression with 30-day mortality as the primary outcome, and patient demographic and clinical data routinely available at presentation as potential predictor variables. We externally validated the rule in 221 inpatients with pulmonary embolism from Switzerland and France.Measurements: We compared mortality and nonfatal adverse medical outcomes across the derivation and two validation samples.Main Results: The prediction rule is based on 11 simple patient ...
974 citations
TL;DR: These data demonstrate a strong association between moderate to severe sleep-disordered breathing and prevalent stroke, independent of confounding factors and provide the first prospective evidence that sleep- Disordered breathing precedes stroke and may contribute to the development of stroke.
Abstract: Rationale: Sleep-disordered breathing has been linked to stroke in previous studies. However, these studies either used surrogate markers of sleep-disordered breathing or could not, due to cross-sectional design, address the temporal relationship between sleep-disordered breathing and stroke.
Objectives: To determine whether sleep-disordered breathing increases the risk for stroke.
Methods: We performed cross-sectional and longitudinal analyses on 1,475 and 1,189 subjects, respectively, from the general population. Sleep-disordered breathing was defined by the apnea–hypopnea index (frequency of apneas and hypopneas per hour of sleep) obtained by attended polysomnography. The protocol, including polysomnography, risk factors for stroke, and a history of physician-diagnosed stroke, was repeated at 4-yr intervals.
Measurements and Main Results: In the cross-sectional analysis, subjects with an apnea–hypopnea index of 20 or greater had increased odds for stroke (odds ratio, 4.33; 95% confidence interval, 1.32–14.24; p = 0.02) compared with those without sleep-disordered breathing (apnea–hypopnea index, <5) after adjustment for known confounding factors. In the prospective analysis, sleep-disordered breathing with an apnea–hypopnea index of 20 or greater was associated with an increased risk of suffering a first-ever stroke over the next 4 yr (unadjusted odds ratio, 4.31; 95% confidence interval, 1.31–14.15; p = 0.02). However, after adjustment for age, sex, and body mass index, the odds ratio was still elevated, but was no longer significant (3.08; 95% confidence interval, 0.74–12.81; p = 0.12).
Conclusions: These data demonstrate a strong association between moderate to severe sleep-disordered breathing and prevalent stroke, independent of confounding factors. They also provide the first prospective evidence that sleep-disordered breathing precedes stroke and may contribute to the development of stroke.
895 citations
TL;DR: Treatment with pirfenidone improved VC and prevented acute exacerbation of IPF during the 9 months of follow-up, and adherence to treatment regimen was similar between pirfenidsone and placebo groups.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without an effective therapy to date. In a double-blind, randomized, placebo-controlled trial, 107 patients were prospectively evaluated for efficacy of a novel compound, pirfenidone. The difference in the change in the lowest oxygen saturation by pulse oximetry (SpO2) during a 6-minute exercise test, the primary endpoint, from baseline to 6 months was not significant between the two groups (p = 0.0722). In a prespecified subset of patients who maintained a SpO2 greater than 80% during a 6-minute exercise test at baseline, the lowest SpO2 improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively). Positive treatment effect was demonstrated in secondary endpoints: (1) change in VC measurements at 9 months (p = 0.0366) and (2) episodes of acute exacerbation of IPF occurring exclusively in the placebo group during the 9 months (p = 0.0031). Significant adverse events were associated with pir...
864 citations
TL;DR: RSV bronchiolitis in infancy severe enough to cause hospitalization is a risk factor for allergic asthma in early adolescence, and the RSV group showed mild airway obstruction both at rest and after bronchodilation, and had slightly more reactive airways.
Abstract: We have prospectively studied wheezing disorder and allergy in 47 children hospitalized with respiratory syncytial virus (RSV) bronchiolitis in infancy and 93 matched control subjects. Subjects with at least three episodes of wheezing were defined as recurrent wheezers and as having asthma if the episodes were doctor verified. Here we report the outcome at age 13 years in 46/47 children with RSV and 92/93 control subjects. Wheezing disorder and clinical allergy were estimated using a questionnaire. Skin prick tests were performed and serum IgE antibodies measured. Spirometry was undertaken at rest, after dry air challenge, and after beta2-agonist inhalation. The occurrence of symptoms over the previous 12 months was significantly higher in the RSV group than among the control subjects, 43% versus 8% for asthma/recurrent wheezing and 39% versus 15% for allergic rhinoconjunctivitis. Sensitization to common inhaled allergens was more frequent in the RSV group than in the control subjects, judged by skin prick tests (50% versus 28%; p = 0.022), or by serum IgE antibodies (45% versus 26%; p = 0.038). Compared with the control subjects, the RSV group showed mild airway obstruction both at rest and after bronchodilation, and had slightly more reactive airways. RSV bronchiolitis in infancy severe enough to cause hospitalization is a risk factor for allergic asthma in early adolescence.
849 citations
TL;DR: In addition to antibiotic therapy, strategies directed toward enhancing host defense and/or limiting excessive inflammation could be important to improve outcome in P. aeruginosa lung infections.
Abstract: Pseudomonas aeruginosa is an important pathogen causing a wide range of acute and chronic infections. P. aeruginosa rarely causes infection in the normal host, but is an efficient opportunistic pathogen causing serious infections in patients who are mechanically ventilated, individuals who are immunocompromised, and patients with malignancies or HIV infection. Among these risk groups, the most vulnerable hosts are neutropenic and patients who are mechanically ventilated. In addition, P. aeruginosa is the most prevalent chronic infection contributing to the pathogenesis of cystic fibrosis. Because of the ubiquitous nature of P. aeruginosa and its ability to develop resistance to antibiotics, it continues to be problematic from a treatment perspective. The pathogenicity of P. aeruginosa is largely caused by multiple bacterial virulence factors and genetic flexibility enabling it to survive in varied environments. Lung injury associated with P. aeruginosa infection results from both the direct destructive effects of the organism on the lung parenchyma and exuberant host immune responses. This article focuses on the major bacterial virulence factors and important aspects of the host immunity that are involved in the pathogenesis of serious P. aeruginosa infection. In addition to antibiotic therapy, strategies directed toward enhancing host defense and/or limiting excessive inflammation could be important to improve outcome in P. aeruginosa lung infections.
758 citations
TL;DR: Investigating the prevalence and incidence of type II diabetes in subjects with SDB found diabetes is more prevalent in SDB and this relationship is independent of other risk factors, however, it is not clear that SDB is causal in the development of diabetes.
Abstract: Rationale: Cross-sectional association has been reported between sleep-disordered breathing (SDB) and insulin resistance, but no prospective studies have been performed to determine whether SDB is causal in the development of diabetes.Objectives: The purpose of our study was to investigate the prevalence and incidence of type II diabetes in subjects with SDB and whether an independent relationship exists between them.Methods: A cross-sectional and longitudinal analysis was performed in 1,387 participants of the Wisconsin Sleep Cohort. Full polysomnography was used to characterize SDB. Diabetes was defined in two ways: (1) physician-diagnosis alone or (2) for those with glucose measurements, either fasting glucose ⩾ 126 mg/dl or physician diagnosis.Measurements and Main Results: There was a greater prevalence of diabetes in subjects with increasing levels of SDB. A total of 14.7% of subjects with an apnea–hypopnea index (AHI) of 15 or more had a diagnosis of diabetes compared with 2.8% of subjects with an ...
737 citations
TL;DR: In this paper, the authors described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never, transient early, persistent and late-onset wheezers.
Abstract: Rationale: The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birth cohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n = 425), transient early wheezers (n = 164), persistent wheezers (n = 113), and late-onset wheezers (n = 124).Objective: We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence.Methods: Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests.Results: The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF25–75 (–259 ml/s, p < ...
651 citations
TL;DR: The ARDS survivors had decreased quality of life, with the physical domains improving at 1 year, with no additional change at 2 years, and role emotional, pain, and general health did not change from hospital discharge to 2 years.
Abstract: Acute respiratory distress syndrome (ARDS) has a high mortality and is associated with significant morbidity. Prior outcome studies have focused predominant on short-term outcomes (6–12 months). We assessed longitudinal neurocognitive, emotional, and quality of life in ARDS survivors at hospital discharge, and 1 and 2 years after hospital discharge using neuropsychologic tests and emotional and quality-of-life questionnaires. Neurocognitive sequelae occurred in 73% (54 of 74) of ARDS survivors at hospital discharge, 46% (30 of 66) at 1 year, and 47% (29 of 62) at 2 years. ARDS survivors report moderate to severe depression (16% and 23%) and anxiety (24% and 23%) at 1 and 2 years, respectively. The ARDS survivors had decreased quality of life, with the physical domains improving at 1 year, with no additional change at 2 years. Role emotional, pain, and general health did not change from hospital discharge to 2 years. Mental health improved during the first year and declined at 2 years. ARDS results in sign...
645 citations
TL;DR: The issues of nanotechnology relevant to the anti-TB drugs are highlighted, which may resolve the problem of nonadherence to prescribed therapy, which is one of the major obstacles in the control of TB epidemics.
Abstract: Nanoparticle-based drug delivery systems have considerable potential for treatment of tuberculosis (TB) The important technological advantages of nanoparticles used as drug carriers are high stability, high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, and feasibility of variable routes of administration, including oral application and inhalation Nanoparticles can also be designed to allow controlled (sustained) drug release from the matrix These properties of nanoparticles enable improvement of drug bioavailability and reduction of the dosing frequency, and may resolve the problem of nonadherence to prescribed therapy, which is one of the major obstacles in the control of TB epidemics This article highlights some of the issues of nanotechnology relevant to the anti-TB drugs
TL;DR: It is hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications.
Abstract: We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications. In a multicenter trial, patients admitted to the Intensive Care Unit (ICU) with severe community-acquired pneumonia received protocol-guided antibiotic treatment and were randomly assigned to hydrocortisone infusion or placebo. Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days. Primary end-points of the study were improvement in Pa(O(2)):FI(O(2)) (Pa(O(2)):FI(O(2)) > 300 or >/= 100 increase from study entry) and multiple organ dysfunction syndrome (MODS) score by Study Day 8 and reduction in delayed septic shock. Forty-six patients entered the study. At study entry, the hydrocortisone group had lower Pa(O(2)):FI(O(2)), and higher chest radiograph score and C-reactive protein level. By Study Day 8, treated patients had, compared with control subjects, a significant improvement in Pa(O(2)):FI(O(2)) (p = 0.002) and chest radiograph score (p < 0.0001), and a significant reduction in C-reactive protein levels (p = 0.01), MODS score (p = 0.003), and delayed septic shock (p = 0.001). Hydrocortisone treatment was associated with a significant reduction in length of hospital stay (p = 0.03) and mortality (p = 0.009).
TL;DR: Bud/form maintenance + relief prolonged the time to first severe exacerbation (p < 0.001), reduced severe exacerbations rate, and improved symptoms, awakenings, and lung function compared with both fixed dosing regimens.
Abstract: Asthma control is improved by combining inhaled corticosteroids with long-acting beta2-agonists. However, fluctuating asthma control still occurs. We hypothesized that in patients receiving low maintenance dose budesonide/formoterol (bud/form), replacing short-acting beta2-agonist (SABA) reliever with as-needed bud/form would provide rapid symptom relief and simultaneous adjustment in antiinflammatory therapy, thereby reducing exacerbations. In this double-blind, randomized, parallel-group study, 2,760 patients with asthma aged 4-80 years (FEV1 60-100% predicted) received either terbutaline 0.4 mg as SABA with bud/form 80/4.5 microg twice a day (bud/form + SABA) or bud 320 microg twice a day (bud + SABA) or bud/form 80/4.5 microg twice a day with 80/4.5 microg as-needed (bud/form maintenance + relief). Children used a once-nocte maintenance dose. Bud/form maintenance + relief prolonged time to first severe exacerbation (p < 0.001; primary endpoint), resulting in a 45-47% lower exacerbation risk versus bud/form + SABA (hazard ratio, 0.55; 95% confidence interval, 0.44, 0.67) or bud + SABA (hazard ratio, 0.53; 95% confidence interval 0.43, 0.65). Bud/form maintenance + relief also prolonged the time to the first, second, and third exacerbation requiring medical intervention (p < 0.001), reduced severe exacerbation rate, and improved symptoms, awakenings, and lung function compared with both fixed dosing regimens.
TL;DR: A retrospective study of 27 patients with COPD with severe pulmonary hypertension among 998 patients who underwent right heart catheterization between 1990 and 2002 as part of a workup for chronic respiratory failure during a period of disease stability.
Abstract: Rationale: Severe pulmonary hypertension occurs occasionally in patients with chronic obstructive pulmonary disease (COPD), but no detailed description of these patients is available. Objectives: To identifyandcharacterizepatientswithCOPDandseverepulmonary hypertension. Methods: Retrospective study of 27 patients with COPD with severe pulmonary hypertension (pulmonary artery mean pressure [Ppa], 40 mm Hg) among 998 patients who underwent right heart catheterization between 1990 and 2002 as part of a workup for chronic respiratory failure during a period of disease stability. Results: Of the 27 patients, 16 had another disease capable of causing pulmonary hypertension. The remaining 11 (11 of 998, 1.1%) patients had COPD as the only cause of pulmonary hypertension, with a median Ppa of 48 mm Hg (interquartile range, 46–50). They had an unusual pattern of cardiopulmonary abnormalities withmildtomoderateairwayobstruction,severehypoxemia,hypocapnia, and a very low diffusing capacity for carbon monoxide (p 0.01 compared with a control group of patients with COPD). Exertional dyspnea was more severe (p 0.01) and survival was shorter (p0.0026)thaninthecontrolsubjects.Conclusions:Severepulmonary hypertension is uncommon in patients with COPD. When it occurs, another cause must be sought. COPD with severe pulmonary hypertension and no other possible cause shares features with pulmonary vascular diseases, such as idiopathic pulmonary hypertension.
TL;DR: Individual variability in several phenotypic characteristics may ultimately determine who develops apnea and how severe the apnea will be and patients may respond to different therapeutic approaches based on the predominant abnormality leading to the sleep-disordered breathing.
Abstract: Considerable progress has been made over the last several decades in our understanding of the pathophysiology of both central and obstructive sleep apnea. Central sleep apnea, in its various forms, is generally the product of an unstable ventilatory control system (high loop gain) with increased controller gain (high hypercapnic responsiveness) generally being the cause. High plant gain can contribute under certain circumstances (hypercapnic patients). On the other hand, obstructive sleep apnea can develop as the result of a variety of physiologic characteristics. The combinations of these may vary considerably between patients. Most obstructive apnea patients have an anatomically small upper airway with augmented pharyngeal dilator muscle activation maintaining airway patency awake, but not asleep. However, individual variability in several phenotypic characteristics may ultimately determine who develops apnea and how severe the apnea will be. These include: (1) upper airway anatomy, (2) the ability of u...
TL;DR: The power of lung hyperinflation as measured by the inspiratory capacity-to-total lung capacity ratio (IC/TLC) to predict mortality in a cohort of 689 patients with chronic obstructive pulmonary disease was analyzed and it was found to be a good and independent predictor of all-cause and respiratory mortality.
Abstract: Static lung hyperinflation has important clinical consequences in patients with chronic obstructive pulmonary disease. We analyzed the power of lung hyperinflation as measured by the inspiratory capacity-to-total lung capacity ratio (IC/TLC) to predict mortality in a cohort of 689 patients with chronic obstructive pulmonary disease (95% males; FEV(1), 1.17 L) with a mean follow-up of 34 months. We also compared the predictive value of IC/TLC with that of the BODE (body mass index, airflow obstruction, dyspnea, exercise performance) Index. Subjects who died (183; 27%) were older; had lower body mass index, FEV(1), and IC/TLC ratio; walked less in the 6-minute walking distance; and had more dyspnea, a higher BODE Index, and comorbidity (p < 0.001). On the basis of logistic regression analysis, IC/TLC was found to be a good and independent predictor of all-cause and respiratory mortality. On the basis of receiver operating characteristic Type II curves, IC/TLC compared favorably with FEV(1) and predicted mortality independently of the BODE Index. We conclude that IC/TLC is an independent risk factor for mortality in subjects with chronic obstructive pulmonary disease. We propose that this ratio be considered in the assessment of patients with chronic obstructive pulmonary disease.
TL;DR: The exhaled breath of patients with lung cancer has distinct characteristics that can be identified with an electronic nose, and the results provide feasibility to the concept of using the electronic nose for managing and detecting lung cancer.
Abstract: Rationale: Electronic noses are successfully used in commercial applications, including detection and analysis of volatile organic compounds in the food industry. Objectives: We hypothesized that the electronic nose could identify and discriminate between lung diseases, especially bronchogenic carcinoma. Methods: In a discovery and training phase, exhaled breath of 14 individuals with bronchogenic carcinoma and 45 healthy control subjects or control subjects without cancer was analyzed. Principal components and canonic discriminant analysis of the sensor data was used to determine whether exhaled gases could discriminate between cancer and noncancer. Discrimination between classes was performed using Mahalanobis distance. Support vector machine analysis was used to create and apply a cancer prediction model prospectively in a separate group of 76 individuals, 14 with and 62 without cancer. Main Results: Principal components and canonic discriminant analysis demonstrated discrimination between samples from patients with lung cancer and those from other groups. In the validation study, the electronic nose had 71.4% sensitivity and 91.9% specificity for detecting lung cancer; positive and negative predictive values were 66.6 and 93.4%, respectively. In this population with a lung cancer prevalence of 18%, positive and negative predictive values were 66.6 and 94.5%, respectively. Conclusion: The exhaled breath of patients with lung cancer has distinct characteristics that can be identified with an electronic nose. The results provide feasibility to the concept of using the electronic nose for managing and detecting lung cancer.
TL;DR: Middle-aged patients with OSA who are free of overt cardiovascular diseases have early signs of atherosclerosis, and all vascular abnormalities correlated significantly with the severity of the OSA, which supports the hypothesis that OSA plays an independent role in Atherosclerosis progression.
Abstract: Background: Obstructive sleep apnea (OSA) is associated with several cardiovascular diseases. However, the mechanisms are not completely understood. Recent studies have shown that OSA is associated with multiple markers of endothelial damage. We hypothesized that OSA affects functional and structural properties of large arteries, contributing to atherosclerosis progression. Methods and Measurements: Twelve healthy volunteers, 15 patients with mild to moderate OSA, and 15 with severe OSA matched for age, sex, and body mass index were studied by using (1) full standard overnight polysomnography; (2) carotid-femoral pulse wave velocity with a noninvasive automatic device; and (3) a high-definition echo-tracking device to measure intima-media thickness, diameter, and distensibility. All participants were free of hypertension, diabetes, and smoking, and were not on any medications. Patients with OSA were naive to treatment. Main Results: Significant differences existed between control subjects and patients wit...
TL;DR: Pulmonary rehabilitation, a multidisciplinary and structured intervention for patients with chronic pulmonary diseases, has been shown to improve exercise tolerance, reduce dyspnea and improve health-related quality of life.
Abstract: Pulmonary rehabilitation, a multidisciplinary and structured intervention for patients with chronic pulmonary diseases, has been shown to improve exercise tolerance, reduce dyspnea and improve health-related quality of life. Pulmonary rehabilitation appears to be cost-effective, since it reduces health care utilization. Exercise training represents the cornerstone of every pulmonary rehabilitation program. To obtain clinically relevant effects, training should closely supervised, of high intensity, lasting 30-45 min for at least 3 days/week. Patients should undertake a minimum of 20 sessions, but longer programs result in larger and more long-lasting effects. Education and self-management programs have been shown to result in a substantial reduction in hospital admissions. Nutritional intervention should be considered for patients who are underweight or those with body composition abnormalities. Patients reporting fear and anxiety may benefit from psychosocial support, and the integration of occupational therapy in a pulmonary rehabilitation program can improve independence in activity. Multidisciplinary pulmonary rehabilitation is preferably implemented in an outpatient hospital- or community-based setting. Inpatient programs are suited for patients with limited transportation capabilities or severe deconditioning. The most convincing effects of home-based rehabilitation are in maintaining the improvements obtained in an outpatient setting.
TL;DR: Regional targeting of inhaled beta2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation and can appreciably enhance inhaled drug therapy and may have implications for developing future inhaled treatments.
Abstract: Rationale: Aerosol particle size influences the extent, distribution, and site of inhaled drug deposition within the airways.Objectives: We hypothesized that targeting albuterol to regional airways by altering aerosol particle size could optimize inhaled bronchodilator delivery.Methods: In a randomized, double-blind, placebo-controlled study, 12 subjects with asthma (FEV1, 76.8 ± 11.4% predicted) inhaled technetium-99m–labeled monodisperse albuterol aerosols (30-μg dose) of 1.5-, 3-, and 6-μm mass median aerodynamic diameter, at slow (30–60 L/min) and fast (> 60 L/min) inspiratory flows. Lung and extrathoracic radioaerosol deposition were quantified using planar γ-scintigraphy. Pulmonary function and tolerability measurements were simultaneously assessed. Clinical efficacy was also compared with unlabeled monodisperse albuterol (15-μg dose) and 200 μg metered-dose inhaler (MDI) albuterol.Results: Smaller particles achieved greater total lung deposition (1.5 μm [56%], 3 μm [50%], and 6 μm [46%]), farther d...
TL;DR: Data from animal models with and without preexisting lung injury, studies of normal human respiratory system mechanics, and the results of five clinical trials of lung-protective mechanical ventilation strategies do not support the commonly held view that inspiratory plateau pressures of 30 to 35 cm H2O are safe.
Abstract: Use of a volume- and pressure-limited mechanical ventilation strategy improves clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, the extent to which tidal volumes and inspiratory airway pressures should be reduced to optimize clinical outcomes is a controversial topic. This article addresses the question, “Is there a safe upper limit to inspiratory plateau pressure in patients with ALI/ARDS?” We reviewed data from animal models with and without preexisting lung injury, studies of normal human respiratory system mechanics, and the results of five clinical trials of lung-protective mechanical ventilation strategies. We also present an original analysis of data from the largest of the five clinical trials. The available data from each of these assessments do not support the commonly held view that inspiratory plateau pressures of 30 to 35 cm H2O are safe. We could not identify a safe upper limit for plateau pressures in patients with ALI/ARDS.
TL;DR: Extent of reticulation and honeycombing on HRCT is an important independent predictor of mortality in patients with IPF.
Abstract: Rationale: High-resolution computed tomography (HRCT) is an integral aspect of the evaluation of patients with suspected idiopathic pulmonary fibrosis (IPF). However, few studies have evaluated its use in a large cohort. Objectives: To describe HRCT features in patients with mild to moderate IPF, compare diagnostic evaluations by a radiology core (three thoracic radiologists) with those by study-site radiologists, correlate baseline clinical and physiologic variables with HRCT findings, and evaluate their association with mortality. Methods: We assessed HRCT scans from patients with IPF (n = 315) enrolled in a randomized controlled study evaluating IFN-γ1b. Measurements and Main Results: There was concordance between study-site and core radiologists regarding the diagnosis of IPF in 86% of cases. Diffusing capacity of carbon monoxide (DLCO) was the physiologic characteristic most highly correlated with HRCT findings. Multivariate analysis identified three independent predictors of mortality: a higher exte...
TL;DR: The age-adjusted incidence rate of TB attributable to reinfection after successful treatment was four times that of new TB, and people who had TB once are at a strongly increased risk of developing TB when reinfected.
Abstract: Rationale: In a high–tuberculosis (TB) incidence area of Cape Town, South Africa, there is a very high rate of unexplained recurrent TB. The incidence of new bacteriologically confirmed disease in the area is 313 per 100,000 individuals. Objective: To estimate the rate of recurrent TB attributable to reinfection after successful treatment. Methods: All patients with reported TB in the area between 1993 and 1998 were followed up to 2001 for disease needing retreatment (recurrences). Patients who were multi-drug–resistant or who had treatment failure, were transferred, or died during treatment were excluded. Analysis was restricted to patients for whom DNA fingerprinting of their Mycobacterium tuberculosis isolates was obtained. Reinfection TB was defined as a recurrent TB episode in which the strains of the separate episodes differed by more than four bands. Measurements and Main Results: 612 of 897 (68%) patients had a DNA fingerprint available at enrollment. Median duration of follow-up was 5.2 years. Re...
TL;DR: It is concluded that CT measurements of airways with a Pi of 0.75 cm or more could be used to estimate the dimensions of the small conducting airways, which are the site of airway obstruction in chronic obstructive pulmonary disease.
Abstract: Chronic obstructive pulmonary disease is characterized by destruction of the lung parenchyma and/or small airway narrowing. To determine whether the dimensions of relatively large airways assessed using computed tomography (CT) reflect small airway dimensions measured histologically, we assessed these variables in nonobstructed or mild to moderately obstructed patients having lobar resection for a peripheral tumor. For both CT and histology, the square root of the airway wall area (Aaw) was plotted versus lumen perimeter to estimate wall thickness. The wall area percentage was calculated as wall area/lumen area + wall area × 100. Although CT overestimated Aaw, the slopes of the relationships between the square root of Aaw and internal perimeter (Pi) measured with both techniques were related (CT slope = 0.2059 histology slope + 0.1701, R2 = 0.32, p < 0.01). The mean wall area percentage measured by CT for airways with a Pi of greater than 0.75 cm predicted the mean dimensions of the small airways with an ...
TL;DR: At the age of 19 years, FEV1 was reduced in subjects with asthma but was similar in smokers and nonsmokers, and smoking and asthma had additive but not multiplier effects on decline.
Abstract: Asthma in adults may be associated with chronic airflow obstruction, possibly resulting from airway disease in early life and/or a greater rate of decline in lung function in adult life compared with those with asthma. Treatment and cigarette smoking may also influence the rate of decline of lung function. The aim of this analysis was to examine the level and rate of decline in lung function in relationship to asthma and cigarette smoking in adults. Subjects (n = 9,317) had participated as adults (> 18 years) in one or more of the cross-sectional Busselton Health Surveys between 1966 and 1981 or in the follow-up study of 1994/1995. The effects of sex, doctor-diagnosed asthma, smoking status, and anthropometric data on the level and rate of decline in FEV1 were examined in a linear mixed effects model. At the age of 19 years, FEV1 was reduced in subjects with asthma but was similar in smokers and nonsmokers. Males, taller subjects, smokers, and subjects with asthma had greater declines in FEV1 with age. Sm...
TL;DR: The results suggest that OSA-related hypoxia and systemic inflammation might be associated with the progression of atherosclerosis and thus might increase the risks of cardiovascular and cerebrovascular morbidity in patients with OSA.
Abstract: Increased carotid intima-media thickness (IMT) and increased serum levels of inflammatory markers, such as C-reactive protein (CRP), interleukin (IL)-6, and IL-18, are associated with an increased risk of cardiovascular and cerebrovascular diseases. The aim of this study was to evaluate whether carotid IMT, a useful marker for early atherosclerosis, is associated with these inflammatory markers in patients with obstructive sleep apnea (OSA). Carotid IMT was investigated with ultrasonography in 36 patients with OSA and 16 obese control subjects. Serum levels of CRP, IL-6, and IL-18 were measured at 5:00 A.M. Carotid IMT (p < 0.001) and serum levels of CRP (p < 0.003), IL-6 (p < 0.005), and IL-18 (p < 0.03) of patients with OSA were significantly higher than those of obese control subjects. Carotid IMT was significantly correlated with serum levels of CRP (r = 0.61, p = 0.0001), IL-6 (r = 0.41, p = 0.01), and IL-18 (r = 0.45, p = 0.005), duration of OSA-related hypoxia (r = 0.60, p = 0.0001), and severity of OSA (r = 0.50, p = 0.002). In addition, the primary factor influencing carotid IMT was duration of hypoxia during total sleep time (p = 0.036). These results suggest that OSA-related hypoxia and systemic inflammation might be associated with the progression of atherosclerosis and thus might increase the risks of cardiovascular and cerebrovascular morbidity in patients with OSA.
TL;DR: It is suggested that FIP may be caused by an interaction between a specific environmental exposure and a gene (or genes) that predisposes to the development of several subtypes of idiopathic interstitial pneumonia.
Abstract: Rationale: Several lines of evidence suggest that genetic factors and environmental exposures play a role in the development of pulmonary fibrosis.Objectives: We evaluated families with 2 or more cases of idiopathic interstitial pneumonia among first-degree family members (familial interstitial pneumonia, or FIP), and identified 111 families with FIP having 309 affected and 360 unaffected individuals.Methods: The presence of probable or definite FIP was based on medical record review in 28 cases (9.1%); clinical history, diffusing capacity of carbon monoxide (DLCO), and chest X-ray in 16 cases (5.2%); clinical history, DLCO, and high-resolution computed tomography chest scan in 191 cases (61.8%); clinical history and surgical lung biopsy in 56 cases (18.1%); and clinical history and autopsy in 18 cases (5.8%).Results: Older age (68.3 vs. 53.1; p < 0.0001), male sex (55.7 vs. 37.2%; p < 0.0001), and having ever smoked cigarettes (67.3 vs. 34.1%; p < 0.0001) were associated with the development of FIP. Afte...
TL;DR: Investigation into therapeutic approaches to inhibit oxidant-mediated reactions in the initiation and progression of pulmonary fibrosis may provide hope for the future treatment of this disease.
Abstract: Idiopathic ulmonary fibrosis (histopathology of usual interstitial pneumonia) is a progressive lung disease of unknown etiology. No treatment has been shown to improve the prognosis of the patients with this disease. Recent evidence, including the observations that the patients with idiopathic pulmonary fibrosis have higher levels of oxidant stress than control patients, and a recent multicenter European study examining the effect of the antioxidant N-acetylcysteine on the progression of idiopathic pulmonary fibrosis suggest that the cellular redox state may play a significant role in the progression of this disease. These complex mechanisms include activation of growth factors as well as regulation of matrix metalloproteinases and protease inhibitors. Potential future approaches for the therapy of interstitial pulmonary fibrosis may involve synthetic agents able to modulate cellular redox state. Investigation into therapeutic approaches to inhibit oxidant-mediated reactions in the initiation and progression of pulmonary fibrosis may provide hope for the future treatment of this disease.
TL;DR: FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms, and is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled antiinflammatory therapy.
Abstract: Rationale: The initial management of patients who present with persistent respiratory symptoms includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a “trial of steroid” to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements. Objectives: We aimed to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed-sequence, placebo-controlled trial of inhaled fluticasone for 4 weeks. Methods: Comparisons of predictive accuracy were made between FENO and other conventional predictors: peak flows, spirometry, bronchodilator response, and airway hyperresponsiveness measured at baseline. “Steroid response” was defined as change in symptoms, peak flows, spirometry, or airway hyperresp...
TL;DR: RBM thickening and the eosinophilic inflammation characteristic of asthma in older children and adults are not present in symptomatic infants with reversible airflow obstruction, even in the presence of atopy.
Abstract: Rationale: We hypothesized that the epithelial reticular basement membrane (RBM) thickening and eosinophilic inflammation characteristic of asthma would be present in symptomatic infants with reversible airflow obstruction. Methods: RBM thickness and numbers of inflammatory cells were determined in ultrathin sections of endobronchial biopsies obtained from 53 infants during clinical bronchoscopy for severe wheeze and/or cough. Group A: 16 infants with a median age of 12 months (range 3.4–26 months), with decreased specific airway conductance (sGaw) and bronchodilator reversibility; Group B: 22 infants with a median age of 12.4 months (5.1–25.9 months), with decreased sGaw but without bronchodilator reversibility; and Group C: 15 infants with a median age of 11.5 months (3.4–24.3 months) with normal sGaw. Additional comparisons were made with the following groups. Group D: 17 children, median age 10.3 years (6–16 years), with difficult asthma; Group E: 10 pediatric control subjects without asthma, median a...