The ratio of FEV₁ to the forced expiratory volume at 6 s of exhalation (FEV₁/FEV₆) has been suggested as a surrogate for the FEV₁/FVC ratio to detect airway obstruction. Current guidelines require that Lower Limit of Normal values be implemented to detect abnormality. In most populations LLN equations are available for FEV₁/FVC but not for FEV₁/FEV₆. We propose a simplified statistical method to approximate reasonably FEV₁/FEV₆ LLN in a population for which FEV₁/FVC LLN are already available.

Spirometric data were collected from 8273 European patients aged 20–85. We computed by Receiver Operator Characteristics analysis the best fit cut-off FEV₁/FEV₆ ratio distributions in function of age and sex for obstruction as diagnosed from FEV₁/FVC LLN values obtained from the relevant reference equations for subjects aged 20–70 and 65–85. We compared the diagnosis of obstruction obtained from these surrogate equations against the reference FEV₁/ FVC LLN diagnosis.

Misdiagnoses from the surrogate equations (FEV₁/FEV₆ = 75.58–0.11 x age for males, and 77.70–0.09 x age for females aged 20–70) were all within 2.3 + 2.0% of the reference LLN. Similar results were found in the 65–85 age group.

The study confirms the feasibility of computing a surrogate LLN equation for the FEV₁/FEV₆ ratio in a population for which accepted FEV₁/FVC LLN already exist. Surrogate equations for FEV₁/FEV₆ may extend the use of the FEV₁/FV₆ ratio for screening and case finding when simplified spirometry is needed.

Flexible bronchoscopy performed through endotracheal tubes (ETT) in mechanically ventilated children can significantly impact ventilation, but the magnitude of this impact has not been established. We used a lung model to simulate mechanical ventilation in a range of child sizes in order to determine how the insertion of pediatric flexible bronchoscopes into ETTs alters ventilatory parameters, especially tidal volume (V_T) and peak inspiratory pressure (PIP) in both healthy and diseased lung models.

We simulated 5 child sizes based on weight, and evaluated 22 bronchoscope/ETT combinations, first in pressure control (PC) ventilation mode and then in volume control (VC) ventilation mode. The combinations ranged from the 2.2 mm (bronchoscope outer diameter)/3.0 mm (ETT-inner diameter) to 5.0 mm bronchoscope/8.0 mm ETT. The primary outcome measures were decrease in tidal volume after bronchoscope insertion during PC ventilation and increase in PIP during VC ventilation

In the PC ventilator mode, V_T decreased by more than 50% with 9 of the combinations, while during VC ventilation, PIP increased to by ≥ 20 cm H2O with 7 combinations. The 2.2 mm scope/3.0 mm ETT, 2.8 mm/5.0 mm, and 3.6mm/5.0 mm combinations severely impaired ventilation, while the 3.6 mm/4.5 mm, 5.0 mm/6.5 mm, and 5.0 mm/7.0 mm combinations were incompatible with adequate ventilation

The insertion of bronchoscopes into ETTs can lead to clinically relevant decreases in V_T when in the PC ventilator mode and large increases in PIP during VC ventilation. The minimum bronchoscope/ETT diameter difference required to maintain adequate ventilation increases with child size.

Adiponectin is associated with asthma. The direction of this association is not known in humans. In mice, this association is bidirectional - allergen inhalation affects serum adiponectin and exogenous adiponectin administration affects asthma. We sought to evaluate whether allergen inhalation affects serum adiponectin in human asthma. Methods: This study included eight sensitized mild asthmatics and six healthy controls. Asthmatics were challenged with inhaled specific allergen (positive allergen skin test), methacholine, and irrelevant allergen (negative allergen skin test). Controls were challenged with irrelevant allergen. Sequential serum samples were obtained before and nine times after each challenge. Serum adiponectin (primary outcome), leptin, adiponectin-to-leptin ratio, eotaxin, and tumor necrosis factor-alpha - response curves, area under the curves, baseline and peak concentrations, were evaluated. Statistical analysis used repeated measures ANOVA and paired t-tests. Results: There were no significant differences in outcome measures among the challenges in asthmatics or when compared to controls. Type II error is an unlikely explanation for these findings since the study was adequately powered to detect changes in serum adiponectin, as reported in the literature. Further, pooled data showed that serum adiponectin diurnal variation curves were lower in asthma than in controls. Conclusions: Serum adiponectin concentrations are lower in asthma than controls. Specific allergen inhalation in asthma does not acutely affect serum adiponectin concentrations. The reverse association i.e. effect of adiponectin on asthma needs further study. If future studies prove adiponectin to be a protective factor for asthma, modulating adiponectin may open a new approach towards managing asthma.

Nearly 30% of all exacerbations of chronic obstructive pulmonary disease (COPD) do not have a clear etiology. Although pulmonary embolism (PE) can exacerbate respiratory symptoms such as dyspnea and chest pain and COPD patients are at a high risk of PE due to a variety of factors including limited mobility, inflammation and co-morbidities, the prevalence of PE during exacerbations is uncertain.

A systematic review of the literature was performed to determine the reported prevalence of PE in acute exacerbations of COPD in patients who do and do not require hospitalization. The literature search was performed using MEDLINE, CINAHL, and EMBASE and complemented by hand searches of bibliographies. Only cross-sectional or prospective studies that used computed tomographic scanning or pulmonary angiogram for PE diagnosis was included.

Of the 2407 articles identified, 5 met the inclusion criteria (sample size, 550 patients). Overall, the prevalence of PE was 19.9% (95% CI, 6.7% to 33.0%; p= 0.014). In hospitalized patients, the prevalence was higher at 24.7% (95% CI, 17.9% to 31.4%; p=0.001) than those who were evaluated in the emergency department (3.3%). Presenting symptoms and signs were similar between patients who did and did not have PE.

One out of four COPD patients who require hospitalization for an acute exacerbation may have PE. A diagnosis of PE should be considered in patients with exacerbation severe enough to warrant hospitalization, especially in those with an intermediate to high pre-test probability of PE.

Lupus pernio is a disfiguring sarcoidosis skin lesion that is difficult to treat and often causes a major psychosocial impact that may adversely affect the patient's quality of life. We reviewed the treatment outcome of 54 patients with lupus pernio who received 118 individual courses of treatment in our Sarcoidosis Clinic.

Methods: Lupus pernio patients were identified from an instution-approved database. All patients were assessed at each clinic visit with facial photographs. By examining the photographs, the percent of the face involved (<10%, 10-25%, >25-50%, >50%) was determined as was the effect of therapy (resolution, near resolution, improvement, no change, worsening). Medications included infliximab-containing regimens (IFX), systemic cortciosteroids (CSS), non-infliximab, non-corticosteroid agents (AG), and CSS+AG.

Results: In terms of achieving resolution or near resolution, IFX regimens were superior to all others (IFX 77%, CSS+AG 29%, CSS 20%, AG 11%; p values of IFX vs other therapies: CSS+AG: 0.0015, CSS: 0.0005, AG: 0.0002). The percent of facial involvement also improved most with IFX. Evaluating a secondary analysis of achieving resolution, near resolution, or improvement, IFX (92%) was superior to AG (20%, p<0.0001) and CSS+AG (56%, p=0.0098) but not CSS (72%, p=0.2456); and AG was inferior to all other regimens.

Conclusions: Infliximab appears superior to systemic corticosteroids with or without additional agents for the treatment of lupus pernio. Non-infliximab, non-cortciosteroid contain regimens are of limited use for this condition.

Sleep disordered breathing occurring during REM sleep (REM SDB) occurs more frequently in women than men. We sought to characterize REM SDB prevalence by gender and age to identify factors that could account for this discrepancy.

Subjects with REM SDB were identified among 2486 patients referred to a university sleep laboratory having an apnea-hypopnea index (AHI)≥5. REM SDB was defined as NREM AHI≤15 and REM AHI to NREM AHI ratio (R:N)≥2. Regression analyses were utilized to determine factors associated with REM SDB.

REM SDB prevalence was 40.8% in women and 21.0% in men. After adjusting for age and obesity, female sex remained a risk factor for REM SDB (odds ratio [OR]=3.0, 95% confidence interval [1.8,4.2]). REM SDB prevalence waned with increasing age in both sexes, such that the odds of having REM SDB fell by 26.7% [15.2%,38.2%] per decade. R:N decreased with age only in women, falling 10.9% [5.5%,16.3%] per decade. NREM AHI in women increased the most with age, 16.0% [11.1%,20.9%] per decade, and least with BMI, 13.0% [9.1%,16.9%] for every 5 unit BMI increase, when compared to REM AHI for women and either index for men.

REM SDB prevalence decreases with age in women as does R:N, perhaps secondary to a disproportionate age-dependent rise in NREM vs. REM AHI in women. Younger women may be protected from SDB during NREM sleep, even in the face of obesity. These patterns may reflect age-related decreases in female hormones.

Little is known about a fairly frequent abnormal pattern of pulmonary function tests, namely a reduced forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) with a normal FEV1/FVC ratio and normal total lung capacity. We term this a nonspecific pattern (NSP). We sought to identify medical conditions having this pattern and to explore mechanisms producing it.

Out of a database of 80,929 tests the NSP was found in 7702 subjects from whom was drawn a random sample of 100 subjects. Medical records and all available tests were examined.

Airway hyperresponsiveness (AHR) and obesity were common. Two groups of subjects were identified. Group A consisted of 68 subjects with evidence of airway disease, including airway hyperresponsiveness and chronic lung disease. A volume derecruitment model was proposed to explain their NSP. Group B consisted of 32 subjects with no evidence of airway disease. Restricted expansion of the thorax or lung may explain the NSP in most of these subjects. Forty subjects had repeated tests and in only 17 were the tests consistently nonspecific.

In a random sample of 100 subjects with the NSP the probable underlying cause of the pattern in 68 subjects was airway disease. In most of the remaining 32 subjects restricted expansion of the thorax or lung may be implicated.

Some endothelin receptor antagonists (ERAs) are associated with liver function test (LFT) abnormalities. However, ambrisentan has an incidence of serum aminotransferases >3 times the upper limit of normal (ULN) similar to that observed in PAH patients who are not taking ERAs. Because ambrisentan may provide benefits in PAH patients who have discontinued ERA therapy due to LFT abnormalities, we evaluated the safety and efficacy of ambrisentan in this patient population.

Patients who previously discontinued bosentan and/or sitaxsentan due to LFT abnormalities received ambrisentan at 2.5mg once daily for 4 weeks followed by 5mg for 8 weeks. The primary endpoint was the incidence of aminotransferases >3xULN considered by the investigator to be related to ambrisentan and resulted in drug discontinuation. Secondary endpoints included aminotransferases >5xULN requiring drug discontinuation and >3xULN requiring dose reduction, as well as changes in 6-minute walk distance (6MWD), Borg dyspnea index (BDI), WHO functional class, and SF-36^® Health Survey score. Patients continued treatment beyond the 12-week endpoint with monthly monitoring of LFTs.

Thirty-six patients who previously discontinued bosentan (n=31), sitaxsentan (n=2), or both (n=3) were enrolled. At baseline, 69.4% of patients were receiving prostanoid and/or sildenafil therapy. No patient had an aminotransferase >3xULN that required ambrisentan discontinuation. One patient had a transient aminotransferase >3xULN that resolved following a temporary dose reduction. No additional aminotransferases >3xULN were observed with long-term treatment (median exposure, 102 weeks), despite dose increases to 10 mg once daily in more than half of the patients. Significant improvements in 6MWD and other efficacy assessments were observed.

Ambrisentan treatment may be an option for patients who have discontinued bosentan and/or sitaxsentan therapy due to LFT abnormalities.

The diagnostic yield of endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration (TBNA) for peripheral pulmonary lesions (PPLs) has not been evaluated. The diagnostic impact of TBNA when the EBUS probe is adjacent to lesions remains to be determined.

A prospective, randomized trial.

Two hundred and two patients with PPLs and positive EBUS findings were enrolled. They were randomly divided into two groups. In the EBUS-CDPs (conventional diagnostic procedures) group (103 patients), both transbronchial biopsy (TBB) and bronchial washing (BW) were performed. In the EBUS-TBNA+CDPs group (99 patients), TBNA, TBB, and BW were performed. The diagnostic yield in each group was compared.

A total of 182 patients (94 in the EBUS-CDPs group and 88 in the EBUS-TBNA+CDPs group) were analyzed. The yield in the EBUS-TBNA+CDPs group (78.4%) was significantly higher than the EBUS-CDPs group (60.6%, p=0.015). Cases in which the EBUS probe was located within the lesions had a significantly higher diagnostic yield (78.3%) than when the EBUS probe was adjacent to them (47.2%, p<0.001). Concerning the three different techniques, TBNA showed the highest diagnostic yield (62.5%), in comparison to TBB (48.9%), and to BW (19.8%). The diagnostic yield of TBNA remained unchanged even when the EBUS probe was adjacent to the lesions (p=0.89). No additional adverse effects were observed in the EBUS-TBNA+CDPs group.

Applying TBNA to EBUS-guided CDPs further increased the diagnostic yield of PPLs without additional risk. The diagnostic advantage of TBNA became more obvious if the EBUS probe was adjacent to the lesions. (ClinicalTrials.gov number, NCT00626587)

No guidelines exist to help physicians determine whether the functional and health-related quality of life (HRQoL) changes observed following treatment of patients with pulmonary arterial hypertension (PAH) represent important benefits. These analyses were undertaken to help define a minimally important difference (MID) in exercise capacity, measured by the 6-minute walk distance (6MWD), and HRQoL, measured by the Short Form-36 (SF-36) questionnaire in patients with PAH.

Data from a 12-week sildenafil study in patients with PAH were used to calculate MIDs for 6MWD and the SF-36 Physical Functioning, Role-Physical, Social Functioning, and Vitality scales, using Effect Size, Standard Error of Measurement, and Standard Error of the Difference approaches. Data from all patients enrolled into the treatment groups in the study were included.

A range of plausible MID estimates, including a score change for SF-36 scales and a change in distance walked in meters for 6MWD, were generated for each endpoint. Mean values were calculated for each outcome and recommended as MIDs for each parameter. Based on these computations, the mean MIDs for the SF-36 Physical Functioning, Role-Physical, Social Functioning and Vitality scales and for 6MWD were 13, 25, 21, and 15 points, and 41 meters, respectively.

This is the first clinical investigation to estimate MIDs for key SF-36 domains and 6MWD in patients with PAH and provides a much needed metric for interpreting the level of change in patients with PAH against which other treatments and trials can be measured.

No score is available to assess severity and stratify mortality risk in ventilator-associated pneumonia(VAP). Our objective is to develop a severity assessment tool for VAP patients.

A prospective, observational, cohort study was performed, including 441 patients with VAP in three multidisciplinary ICUs. Multivariate logistic regression was performed to identify variables independently associated with ICU mortality. Results were converted into a 4-variable score based on the PIRO concept for ICU mortality risk stratification in VAP patients.

A severity assessment score was developed including the presence of the following variables: Comorbidities (COPD, immunocompromise, heart failure, cirrhosis or chronic renal failure); bacteremia; systolic BP<90mmHg, and ARDS. A simple, 4-variable VAP PIRO score was obtained at VAP onset. Mortality varied significantly according to VAP PIRO score(p<0.001). On the basis of observed mortality for each VAP PIRO score, patients were stratified into 3 levels of risk: a)Mild;0-1 points, b)High;2 points, c)Very high;3-4 points. VAP PIRO score was associated with higher risk of death in Cox regression analysis in high(HR 2.14 95%CI 1.19-3.86) and very high risk group(HR 4.63 95%CI 2.68 – 7.99). Moreover, medical resource use after VAP diagnosis was higher in high and very high risk levels compared to patients in mild risk level, evaluated using length of ICU stay(22.0±10.6 vs 18.7±12.8 days, p<0.05) and duration of mechanical ventilation(18.3±10.1 vs 15.1±11.5 days, p<0.05).

VAP PIRO score is a simple, practical clinical tool for predicting ICU mortality and health care resources use that is likely to assist clinicians in determining VAP severity.

High cortisol levels are frequent in patients with severe infections. However, the predictive value of total cortisol and of the presence of critical illness related corticosteroid insufficiency (CIRCI) in severe community-acquired pneumonia (CAP) remains to be thoroughly evaluated. The aim of this study was to investigate the predictive value of adrenal response in patients with severe CAP admitted to the ICU.

Baseline and post-corticotropin cortisol levels C-reactive protein, D-dimer, clinical variables, SOFA, APACHE II and the CURB-65 score were measured in the first 24 hours. Results are shown as median (25%-75% interquartile range (IQR). The major outcome measure was hospital mortality.

Seventy-two patients with severe CAP admitted to the ICU were evaluated. Baseline cortisol levels were 18.1 (14.4-26.7) µg/dL and delta cortisol after 250µg of corticotropin was 19 (12.8-27) µg/dL. Baseline cortisol levels presented positive correlations with scores of disease severity including CURB-65, APACHE II and SOFA (P <0.05). Cortisol levels in non-survivors were higher than in survivors. CIRCI was diagnosed in 29 (40.8%) patients. In univariate analysis, baseline cortisol, CURB-65 and APACHE II were predictors of death. The discriminative ability of baseline cortisol [Area under ROC curve=0.77 (95% CI, 0.65-0.90) - best cutoff for cortisol was 25.7µg/dL] for in-hospital mortality was better than APACHE II, CURB-65, SOFA, D-dimer or C-reactive protein.

Baseline cortisol levels are better predictors of severity and outcome in severe CAP than post-corticotropin cortisol or routinely measured laboratory parameters or scores as APACHE II, SOFA and CURB-65.

High cortisol levels are present in a significant proportion of patients with severe community-acquired pneumonia. In these patients, cortisol has the ability to predict mortality and correlates with disease severity. Prognostic performance of total baseline cortisol is better than APACHE II, CURB-65, D-dimer, delta cortisol and C-reactive protein.

The aim was to investigate the significance of snoring and sleep apnea on daytime symptoms in a population-based sample of women.

From the general population, 400 women, aged 20-70 years, were randomly selected, with over sampling of habitually snoring women. They were investigated with a full-night polysomnography and a questionnaire. The apnea-hypopnea index (AHI) was calculated, and women who acknowledged snoring loudly and disturbingly often or very often were considered habitual snorers.

Habitual snoring was independently related to excessive daytime sleepiness, OR= 2.28 (1.31-3.99), to falling asleep involuntarily during the day, OR= 2.11 (1.06-4.21), to waking up unrefreshed, OR= 2.14 (1.30-3.52), to daytime fatigue, OR= 2.77 (1.54-4.99) and to a dry mouth on awakening, OR= 2.00 (1.22-3.27) after adjustment for of AHI, age, body mass index (BMI), smoking, total sleep time, % slow wave sleep and % REM sleep. Apnea-hypopnea index ≥15 was only related to a dry mouth on awakening after adjustment for snoring, age, BMI, smoking, total sleep time, % slow wave sleep and % REM sleep, OR= 2.24 (1.14-4.40). An AHI of 5-15 was not related to any daytime symptom.

Excessive daytime sleepiness and daytime fatigue are related to habitual snoring independent of the apnea-hypopnea frequency, age, obesity, smoking and sleep parameters in a population-based sample of women, but not to the apnea-hypopnea index. This indicates that snoring is an independent cause of excess daytime sleepiness and not merely a proxy for sleep apnea.

Exercise-induced bronchoconstriction (EIB) in the asthmatic child is associated with persistent airway inflammation and poor disease control. EIB could arise partly from airway-oxidative stress. Exhaled breath condensate (EBC) levels of 8-Isoprostane (8-IsoP) – a known marker of oxidative stress – might therefore be helpful for monitoring asthma noninvasively.

We recruited 46 asthmatic children and adolescents aged 6-17 yrs (29 boys) all of whom underwent lung-function testing, FE_NO measurements and collection of EBC for 8-IsoP measurement before and after exercise challenge. FE_NO was measured before and 5 and 20 min after exercise. Spirometry was repeated 1, 5, 10, 15 and 20 minutes after exercise.

Baseline 8-IsoP (but not baseline FE_NO levels) correlated with the fall in forced expiratory volume in 1 second (FEV₁) 5 min after exercise (r= -0.47, p=0.002). 8-IsoP levels measured after exercise remained unchanged from baseline; conversely, FE_NO levels decreased in parallel with the decline in FEV₁ at 5 min (r=0.44, p=0.002). Mean baseline 8-IsoP concentrations were higher in patients with EIB (n = 12) than in those without (n = 34) (44.9 pg/mL, 95% CI 38.3-51.5; vs 32.3 pg/mL, 95% CI 27.6-37.0; p<0.01). No difference was found in baseline FE_NO between groups (EIB: 38.7 ppb, 95% CI 24.5-61.1; without EIB: 29.1 ppb, 95% CI 22.0-38.4).

Increased 8-IsoP concentrations in the EBC of asthmatic children and adolescents with EIB suggest a role of oxidative stress in bronchial hyperreactivity.

Childhood idiopathic bronchiectasis (IB) unrelated to cystic fibrosis (CF) or known immunodeficiency remains a common problem among indigenous populations in developed and developing countries. The physical and transport properties of sputum among children with IB have not been described and these properties may suggest therapies that would be particularly effective for this group of children.

Sputum from children with stable IB and chronic daily productive cough was collected to measure viscosity, elasticity, cohesivity, adhesivity, and mucociliary and cough transportability in vitro. Results were compared to banked data from sputa of children with cystic fibrosis (CF) and adults with chronic bronchitis (CB) measured by the same methods.

Sputa from children with CF and adults with CB had similar values for viscosity, elasticity, frictional adhesion, cough transportability and mucociliary transportability. The elasticity of sputum from children with IB was 12-20% of the value of CB and CF sputum respectively.(P<.01) The viscosity of sputum from children with IB was 23-32% the value of CB and CF sputum respectively (p<.02) Surface frictional adhesion for sputum from children with IB was 55% of the values from both CF and CB sputa. (p<.0001). Cough transportability for sputum from children with IB was 43-54% greater than for sputum from CB and CF patients respectively. (P<.0001) Mucociliary transportability was similar for all three groups. (p>.05)

Physical and transport properties of sputum from children with IB who are stable in the outpatient setting are substantially different and lead to improved cough transportability compared to sputum from children with cystic fibrosis or adults with chronic bronchitis. Therapies that focus on cough may be sufficient to improve airway mucus clearance in children with IB. Sputum properties may explain in part the different clinical course of children with IB compared to children with CF.

Although cigarette smoking is the most important risk factor for COPD, only a minority develop COPD, suggesting the significant genetic role. To solve the underlying pathophysiologic mechanism, it is critical to understand genes and their final product, i.e., proteins. We investigated the exclusive proteins from the lung tissues obtained from COPD patients using proteomics.

Non-tumorous lung tissue specimens were obtained from patients who underwent surgery for lung cancer. We included 22 subjects: nonsmokers (n = 8), smokers without COPD ("healthy smokers"; n = 7), and smokers with COPD ("COPD"; n = 7). Proteins were separated their spots with 2-DE, and examined by MALDI-TOF. To validate the proteins from above procedures, Western blotting and immunohistochemistry were conducted.

Twelve protein spots from COPD group, showing significantly increased or decreased compared with the other two groups, were chosen for MALDI-TOF analysis. Eight proteins were up-regulated in the COPD group as compared with the nonsmokers. Meanwhile, 5 proteins from the COPD group were up-regulated, and 5 down-regulated when compared with the healthy smokers. Of these, MMP-13 and thioredoxin-like 2 were significantly increased in the COPD patients by Western blot and immunohistochemistry. MMP-13 was mainly expressed in the alveolar macrophages and type II pneumocytes. On the other hand, thioredoxin-like 2 was primarily seen in the bronchial epithelium.

MMP-13 and thioredoxin-like 2 in lungs increased in patients with COPD. MMP-13 was mainly expressed in the alveolar macrophages and type II pneumocytes. In contrast, thioredoxin-like 2 was primarily seen in the bronchial epithelium.

Severe diaphragmatic dysfunction can prolong mechanical ventilation after cardiac surgery. An ultrasonographic criterion for diagnosing severe diaphragmatic dysfunction defined by a reference technique such as transdiaphragmatic pressure measurements has never been determined.

Twenty-eight patients requiring mechanical ventilation >7 days post-operatively were studied. Esophageal and gastric (Pga) pressures were measured to calculate transdiaphragmatic pressure during maximal inspiratory effort (Pdi_max) and the Gilbert index (Pga/Pdi), which evaluates the diaphragm contribution to respiratory pressure swings during quiet ventilation. Ultrasonography allowed measuring hemidiaphragmatic excursions during maximal inspiratory effort (E_right, E_left). Best Ewas the greatest positive value from either hemidiaphragm. Twenty cardiac surgery patients with uncomplicated post-operative course were also evaluated with ultrasonography pre and post-operatively. Measurements were performed in semi-recumbent position.

Pdi_max was below normal value in 27 of the 28 patients with prolonged mechanical ventilation (median [interquartile range]: 39[28] cm H₂O). Eight patients had Gilbert indices ≤0 indicating severe diaphragmatic dysfunction. Best E was lower in patients with Gilbert index ≤0 than >0 (30[10] vs. 19[7] mm respectively, p=0.001). Best E <25mm had a positive likelihood ratio of 6.7 (95% confidence interval 2.4-19) and a negative likelihood ratio of 0 (95% confidence interval 0-1.1) for having a Gilbert index ≤0. None of the patients with uncomplicated course had Best E <25mm either pre or post-operatively.

Ultrasonographic-based determination of hemidiaphragm excursions in patients requiring prolonged mechanical ventilation after cardiac surgery may help identify those with and without severe diaphragmatic dysfunction as defined by the Gilbert index.

Although the cycle ergometer is the traditional mode for exercise testing in patients with respiratory disease, this preference over the treadmill does not consider perceptual responses. Our hypotheses were: 1) the regression slope between breathlessness and oxygen consumption (VO₂) is greater on the treadmill than on the cycle ergometer; and 2) the regression slope between leg discomfort and VO₂ is greater on the cycle ergometer than on the treadmill.

Twenty patients (10 men/10 women) with chronic obstructive pulmonary disease (COPD) (mean [± SD] post-bronchodilator FEV₁, 50 ± 15 % predicted) used a continuous method to report changes in breathlessness and in leg discomfort during cycle and treadmill exercise.

Patients reported an earlier onset of breathlessness and leg discomfort during cycling. Peak ratings of breathlessness were higher on the treadmill, whereas peak ratings of leg discomfort were higher on the cycle ergometer. The regression slopes for breathlessness as a function of VO₂ and of minute ventilation (V_E) were higher on the treadmill. The regression slopes between leg discomfort and VO₂ were similar for treadmill and cycle exercise. Peak VO₂ was significantly higher with treadmill exercise (mean = 8%; p = 0.002).

Patients with COPD exhibit different perceptual and physiological responses during treadmill walking and cycling. Although ratings of breathlessness are initially higher with cycling at equivalent levels of VO₂, the changes in breathlessness as a function of physiological stimuli (VO₂ and V_E) are greater during treadmill exercise. Leg discomfort is the predominant symptom throughout cycling.

Thoracotomy is associated with severe pain. We hypothesized that the concomitant use of a subanesthetic dose of ketamine plus a 2/3-standard morphine dose might provide more effective analgesia with fewer side effects than a standard morphine dose for early pain control.

We conducted a 6-month randomized, double blind study in patients undergoing thoracotomy for minimally invasive direct coronary artery bypass or for lung tumor resection. After extubation, when objectively awake (≥5/10 VAS) and complaining of pain (≥5/10 VAS), patients were connected to a PCIA delivering 1.5mg morphine/bolus (MO group) or 1.0mg morphine+5mg ketamine/bolus (MK group), with a 7-minute lockout time. Rescue intramuscular diclofenac 75mg was available. Follow-up lasted 4h.

Forty-one patients completed the study. MO patients (n=20) used 6.8±1.9 (mean±SD) and 5.5±3.6 mg/h morphine during h 1 and 2, respectively; MK patients (n=21) used 3.7±1.2 and 2.8±2.3 mg/h, respectively (P<0.01). The 4-h activation rate of the device was double in the MOs than the MKs (66 ± 54 vs. 28 ± 20, P<0.001). The maximal self-rated pain score was 5.6±1.0 for the MO vs. 3.7±0.7 for the MK group (P<0.01). Four MO patients vs. one MK required diclofenac; 6 MO but no MK patients had SpO₂ <94% on a FiO₂=0.4 (P<0.01); two MO patients required re-intubation. PaCO₂ was higher in the MO group (40±6 vs. 33±5 mmHg, P<0.05). Heart rate, blood pressure and incidence of nausea/vomiting were similar; no ketamine-related hallucinations were detected.

Subanesthetic ketamine combined with a 35%-lower morphine dose provided equivalent pain control compared to the standard morphine dose alone, with fewer adverse side effects and a 45%-reduction in morphine consumption.

Registered at this site ClinicalTrials.gov; Registration number NCT00625911

Approximately 15% of COPD, including chronic bronchitis, is attributable to occupational exposures. An occupational history is essential to identify exposures responsible for work related chronic bronchitis.

We conducted a structured retrospective analysis of the medical records of veterans, age 18-70 years, newly diagnosed with chronic bronchitis in order to: 1) assess the quality of documented occupational histories, and 2) characterize the management of patients with a history of exposure to a potentially hazardous respiratory substance. We also analyzed occupational exposure data reported by patients on a structured questionnaire.

60 patients were included in the final analysis. 6150 notes were reviewed. Occupational status was documented in the records of 54 (90%) patients. A description of occupational duties was recorded in 32 (53%) records and work exposure data in 26 (43%). Clinicians concluded occupational exposures potentially contributed to chronic bronchitis in 3 (5%) patients. A recommendation for exposure avoidance was documented for 6 (10%) patients. On questionnaire, most patients reported a history of occupational exposure to respirable substances and most reported symptoms of cough and/or shortness of breath.

Details about job duties and occupational respiratory exposures were documented in the records of approximately half of patients with newly diagnosed chronic bronchitis. Patient self-reports of occupational exposures and respiratory symptoms were common. A determination that occupational exposures contributed to chronic bronchitis was rare. Few patients were counseled to take measures to avoid occupational exposures. Work related chronic bronchitis may be incompletely assessed and under managed by clinicians.

Asthma is one of the most prevalent chronic medical conditions in the United States (U.S.). Asthma's relationship with psychological factors has been known for centuries and recently there has been a resurgence of interest in this topic. This study investigates the relationship between current asthma and poor mental health in a nationally representative sample of the U.S. population.

This study utilizes data from the 2006 Behavioral Risk Factor Surveillance System (BRFSS) survey (n = 355,710). A multinomial logistic regression model was constructed to assess the relationship between current asthma and poor mental health. The relationship between formerly having asthma and poor mental health was also investigated.

Persons reporting poor mental health have increased risk of currently having asthma compared to persons reporting good mental health. Additionally, this asthma-mental health relationship has a "dose-response" relationship. For every incremental increase in days of poor mental health, there is a corresponding increase in risk of currently having asthma. Previously reported risk factors for asthma, i.e. age, gender, race, marital, smoking, overall health, exercise, obesity, and socio-economic (SES) status were all found to be important covariates of asthma. The relationship between former asthma and poor mental health is less clear.

This large, nationally representative sample confirms the relationship between asthma and mental health symptoms. Any degree of poor mental health appears to increase one's risk for asthma. Future research is needed to determine the causal and/or physiological relationship between asthma and mental health symptoms.

Some patients with advanced pulmonary arterial hypertension (PAH) develop thrombocytopenia while receiving intravenous epoprostenol therapy. In this study we evaluate whether epoprostenol use, other PAH medication use, hemodynamics or PAH etiology are associated with thrombocytopenia in PAH.

Platelet counts were evaluated in 47 PAH patients receiving intravenous epoprostenol, and in 44 patients with an inadequate response to initial therapy with oral agents in a cross-sectional study. Associations between thrombocytopenia (platelet count <150,000) and epoprostenol use, hemodynamics, PAH etiology and use of other PAH medications were evaluated in univariable and multivariable analyses.

PAH subtypes included idiopathic (69%), fenfluramine (18%), connective tissue disease (10%) and congenital heart disease (2%) associated PAH. Thrombocytopenia was observed in 34% of patients treated with epoprostenol compared with 15% of patients receiving oral therapy (OR 2.9, p<0.05), and the association between epoprostenol and thrombocytopenia remained significant after adjustment for differences in hemodynamics (OR 5.0, p<0.05). Right atrial pressure (OR 1.12 per mm Hg, p<0.05) and mixed venous oxygen saturation (SVO2, OR 0.92 per %, p<0.05) were also associated with thrombocytopenia in univariable analyses, and after logistic regression analysis, both use of epoprostenol (OR 5.2, p<0.01) and SVO2 (OR 0.89, p<0.01) were independently associated with thrombocytopenia. In a separate analysis including only patients with current or prior epoprostenol use, epoprostenol dose and right atrial pressure were inversely associated with platelet count.

Epoprostenol use and severity of hemodynamic abnormalities are associated with thrombocytopenia in PAH, and these effects appear to be independent and additive.

Chronic Mountain Sickness (CMS) is characterized by a loss of adaptation to hypoxia in high altitude dwellers. Patients develop chronic hypoxemia, excessive erythrocytosis and frequently pulmonary hypertension, which may lead to cardiac failure. We sought to assess the determinants of cardiac function in CMS patients with hypoxia-induced pulmonary hypertension

Fifteen healthy men living at sea level (SL) were compared to 15 healthy men living at high altitude (HA) and 55 patients with CMS (CMS) from Cerro de Pasco, Peru (4,300 m). Pulmonary pressures and cardiac function were estimated by echocardiography.

None of the subjects had overt cardiac failure symptoms. CMS patients exhibited elevated pulmonary pressures as assessed by high tricuspid pressure gradients (34 ± 10 mmHg for CMS vs. 25 ± 4 mmHg for HA p = 0.002 and 19 ± 3 mmHg for SL p < 0.001). They also showed right ventricular dilation (end-diastolic right ventricular area: 17 ± 2 cm² for CMS vs. 13 ± 2 cm² for HA and 12 ± 2 cm² for SL, p < 0.001) but did not display impaired systolic ventricular function. However, right ventricular Tei index was increased in altitude subjects (0.56 ± 0.15 for CMS, 0.52 ± 0.12 for HA vs. 0.21 ± 0.12 for SL, p < 0.001).

Despite obvious pulmonary arterial hypertension and right heart dilation, CMS patients did not show any symptom or echocardiographic parameter of heart failure.

The highly active antiretroviral therapy (ART) era (1996-present) has been associated with improved survival among HIV-infected outpatients, but ICU data from 2000-present are limited.

We conducted a retrospective study of HIV-infected adults admitted to the ICU at San Francisco General Hospital (2000-2004). The primary outcome was survival to hospital discharge.

During the 5-year study period, there were 311 admissions for 281 patients. Respiratory failure remained the most common indication for ICU admission (42% overall), but the proportion of patients with respiratory failure decreased each year from 52% to 34% (p = 0.02). Hospital survival rates significantly increased during the 5-year period (p = 0.001). ART use at admission was not associated with survival, but it was associated with higher CD4 cell counts, lower plasma HIV RNA levels, higher serum albumin, and lower proportions of AIDS-associated admission diagnoses and PCP. In multivariate analysis, a higher serum albumin level (Adjusted Odds Ratio, AOR = 2.08, 95% Confidence Interval, CI = 1.41-3.06, p = 0.002) and absence of mechanical ventilation (AOR = 6.11, 95% CI = 2.73-13.72, p < 0.001) were associated with survival.

In this sixth in a series of consecutive studies started in 1981, we found that the epidemiology of ICU admission diagnoses continues to change. Our study also found that survival for critically ill HIV-infected patients continues to improve in the current era of ART. Although ART use was not associated with survival, it was associated with predictors that were associated with survival in multivariate analysis.

Nitric oxide (NO) is produced by resident and inflammatory cells in the respiratory tract by the enzyme NO synthase (NOS), which NOS exists in three isoforms: neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). NO production is increased in patients with COPD and the production of NO under oxidative stress conditions generates reactive nitrogen species that may amplify the inflammatory response in COPD.

To examine the role of increased NO in COPD, we administered a relatively selective iNOS inhibitor, aminoguanidine (AG), by nebulization in a double-blind, placebo-controlled study in COPD patients, healthy smokers and healthy non-smoking subjects. We investigated whether AG had any effect on exhaled NO produced in the central (J_NO) and peripheral lungs (C_alv), on NO metabolities (nitrite/nitrate, peroxinitrite, nitrotyrosine) and on a marker of oxidative stress (8-isoprostane) in exhaled breath condensate (EBC) and in sputum.

AG administration resulted in a significant reduction in J_NO compared with administration of the saline solution control in healthy subjects, smokers and COPD patients. C_alv in smokers and in COPD patients was not completely inhibited one hour after AG inhalation, in marked contrast to previous results in asthma. Moreover, peroxynitrite, nitrite/nitrate levels were also increased in EBC and in sputum of smokers and COPD and were not completely inhibited following AG inhalation. 8-isoprostane levels were also increased in smokers and in COPD patients but were not reduced after AG inhalation.

These results suggest that cNOS isoform as well as iNOS might be involved in NO release and contribute to the high C_alv and peroxynitrite production in COPD.

The literature on preoperative smoking cessation indicates that smoking patients are more likely to have postoperative complications. However, the economic implications of such complications are unclear. In particular, the balance between the cost of a preoperative intervention for smoking cessation (PISC) and the benefit resulting from the potential decrease in hospitalization costs is not known.

Only one previous study, a randomized trial involving smokers scheduled for hip or knee replacement surgery (Møller A et al, Lancet, 2002;359:114-17), provides sufficient data to simulate the hospital course of patients either subjected to a PISC or not. We used a multi-state Markov-type model and official French hospital costs for 2008 to simulate this situation. The cost-benefit analysis adopted the payer's perspective.

The mean benefit, corresponding to the decrease in the cost of the hospital stay for a reference case patient having followed a PISC, was estimated at 313 euros, with a corresponding mean cost of the PISC estimated at 196 euros. Therefore, the PISC was associated with a cost saving of 117 euros per patient. The results were most sensitive to the cost of ICU care as a proxy for cost of smoking related complications, and to the relative risk of complication between patients with and without a PISC.

Under the conditions simulated by this cost-benefit model, potential modest cost savings may accrue with implementation of an institution-based smoking cessation program through reduced total hospitalization costs that exceed the cost of the intervention.

Pulmonary hypertension is a common cause of functional tricuspid regurgitation (TR), but other factors play a role in determining TR severity. The objectives of our study were to determine the distribution of TR severity in relation to pulmonary artery systolic pressure (PASP) and to define the determinants of TR severity.

The echocardiographic reports and selected echocardiographic studies of patients with echocardiographic estimation of PASP were reviewed. Patients with organic tricuspid valve disease were excluded from analysis.

Among 2139 patients, the frequency of moderate or severe TR was progressively greater in patients with higher PASP. Nevertheless, TR was only mild in a substantial proportion of patients with high PASP (65.4% and 45.6% of patients with PASP 50-69 mmHg and ≥ 70 mmHg, respectively). By multivariate analysis – age, female gender, PASP (odds ratio: 2.26 per 10 mmHg increase, 95% confidence interval: 1.95-2.61), pacemaker lead, right atrial and right ventricular enlargement, left atrial enlargement, and organic mitral valve disease were independently associated with greater degrees of TR. In patients with PASP ≥ 70 mmHg, right atrial size, tricuspid annular diameter, and tricuspid valve tethering area were greater in patients with greater degrees of TR.

PASP is a strong determinant of TR severity, but many patients with pulmonary hypertension do not exhibit significant TR. In addition to PASP, demographic characteristics, mechanical factors, remodeling of the right heart cavities, and other factors (possibly reflecting the presence of atrial fibrillation or occult organic TV disease) are predictive of TR severity.

The role of different risk factors for bronchial hyper-responsiveness (BHR), as gender, atopy, IgE and environmental factors (smoking, occupational exposure, infections), has been described. Indoor and outdoor pollution play an important role too, but few studies analyzed the association with BHR. The aim of this study was to assess the effect of urban residence on BHR.

We studied two general population samples enrolled in two cross sectional epidemiological studies carried out in Northern Italy (Po Delta, rural area) and Central Italy (Pisa, urban area). We analyzed 2760 subjects with an age range of 8-74 years. We performed analysis of variance and logistic regression analysis, using ln slope of the dose-response curve of the methacholine challenge test as dependent variable, and sex, age, smoking habits, respiratory symptoms, results of prick test, IgE value, residence, airway caliber as independent variables.

The mean value of ln slope of the dose-response curve, adjusted for initial airways caliber (by baseline forced expiratory volume in 1 second % predicted value), was significantly higher in females, in smokers, in subjects with respiratory symptoms, in younger and older ages, in subjects with high values of IgE, and in those with positive prick test. After controlling for the independent effects of all these variables, living in urban area was an independent risk factor for having bronchial hyper-responsiveness (OR 1.41, CI 95% 1.13-1.76).

living in urban area is a risk factor for increased bronchial responsiveness.

Pulmonary complications following injury significantly contribute to subsequent mortality. Obese patients have preexisting risk factors for pulmonary complications, and are at risk for these complications following elective surgery. Whether or not obesity contributes to pulmonary complications after critical injury is poorly understood.

A secondary analysis of a prospective cohort study of critically injured adults requiring at least 48 hours of intensive care was performed. Patients were classified into the following body mass index (BMI) groups: ≤ 18.5 kg/m² (underweight), 18.5 to 24.9 kg/m² (normal), 25 to 29.9 kg/m² (overweight), 30.0 to 39.9 kg/m² (obese) and ≥ 40.0 kg/m² (severely obese). Outcomes included the rates of acute respiratory distress syndrome (ARDS) and pneumonia, placement of a tracheostomy, and in-hospital mortality.

1,291 patients were available for analysis, and 30% of these patients were classified as either obese or severely obese. The age, gender and severity adjusted rate of ARDS was lower in severely obese patients (OR 0.36, 95% CI 0.13 – 0.99) as compared to normal weight patients. The rates of pneumonia (37%), tracheostomy (10%) and in-hospital mortality (11%) did not differ between groups. Despite no difference in pulmonary complications, the severely obese group had an ICU length of stay that was 4.8 days (95% CI 1.8 – 7.7) longer than the normal weight group

Obesity does not appear to be an independent risk factor for increased pulmonary complications after critical injury, but severely obese patients are likely to require longer ICU stays.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of ventilator-associated pneumonia (VAP). This prospective, open-label, multicenter clinical trial compared the early microbiologic efficacy of linezolid with that of vancomycin in patients with MRSA VAP.

149 patients with suspected MRSA VAP were randomized to receive either linezolid 600 mg or vancomycin 1 gm q12h. Patients with baseline bronchoscopic bronchoalveolar lavage (BBAL) quantitative culture positive for MRSA (≥ 10⁴cfu/mL) comprised the study population. Primary outcome was microbiologic response (≤ 10²cfu/mL) in a second BBAL performed 72–96 h following start of treatment.

30 linezolid- and 20 vancomycin-treated patients had microbiologically confirmed MRSA at baseline; 23 and 19 patients underwent repeat BBAL, respectively. While a greater number of linezolid patients than vancomycin patients achieved microbiologic cure (56.5% vs 47.4%; p = 0.757; 95% CI, -21.1, 39.4), this difference was not statistically significant. Nonstatistically significant differences were also seen for linezolid versus vancomycin in clinical cure (66.7% vs 52.9%), survival rate (86.7% vs 70.0%), mean duration of ventilation (10.4 vs 14.3 d), hospitalization (18.8 vs 20.1 d), ICU stay (12.2 vs 16.2 d), and days alive and off mechanical ventilation (15.5 vs 11.1 d), respectively. Three patients extubated prior to repeat BBAL had been randomized to linezolid.

Early microbiologic cure rates were not statistically significantly higher with linezolid than with vancomycin despite trends in all secondary clinical outcomes favoring linezolid. These results suggest that any beneficial effect of linezolid may be due to factors other than increased bacterial clearance.

NCT00572559

Hematopoietic-cell-kinase (Hck) is a myeloid cell specific tyrosine kinase, known to induce neutrophil infiltration to the lungs. Although the over-expression of Hck causes emphysema-like histological changes in mouse, its expression and activity in patients with chronic obstructive pulmonary disease (COPD) are unclear.

The aim of this study is to clarify the expression and activity of Hck in neutrophils from COPD patients, and to investigate the association between the degree of Hck expression and the lung function parameters in COPD. Peripheral blood neutrophils were isolated from 22 patients with COPD and 9 healthy subjects (HS). The protein level of Hck and phosphorylated-Hck (p-Hck) were assessed, and the correlation with various background characteristics was evaluated.

The Hck protein level was significantly higher in the neutrophils from COPD patients compared with HS (COPD = 1.094, HS = 0.801, p < 0.05). A significant positive correlation was observed between the protein level of Hck and the surface expression of integrin molecule, CD-11b (r = 0.540; p < 0.01), or CXC chemokine receptor-1 (r = 0.432; p < 0.05). In contrast, there was no difference in the phosphorylation of Hck protein between COPD patients and HS.

The Hck protein level in peripheral blood neutrophils was increased in COPD patients, suggesting that Hck might have an important role in the neutrophil function and play a key role in COPD pathophysiology.

The Burden of Obstructive Lung Disease (BOLD) initiative provides a standardized way of measuring the prevalence of chronic obstructive pulmonary disease (COPD).

We used the BOLD survey to estimate the prevalence of COPD in adults aged 40 years and older in a target population of 325,000 in Southeastern Kentucky. Testing was done at survey centers and homes and included questionnaires on respiratory symptoms, risk factors for COPD and health status. Post bronchodilator spirometry was used to classify subjects. We determined the prevalence of COPD along with the relation of COPD and comorbid disease and physical and mental quality of life measures.

The final study population was 508, with a participation response rate of 25.2%. Overall, 19.6% of subjects met criteria for GOLD stage 1 or higher COPD, and an additional 17.6% met criteria for restriction. Diabetes, heart disease and hypertension were significantly increased among subjects with restriction. Physical quality of life was significantly decreased in all respiratory impairment categories, compared to normals, whereas mental quality of life measures were not affected.

In this population respiratory impairment is highly prevalent and associated with comorbid disease and physical, but not mental, dysfunction.

It remains unknown whether bacteremia and rapid radiological progression of pulmonary infiltrates increase the risk of shock and mortality in ICU patients with Community-acquired pneumonia (CAP). The objective of this study was to investigate the relative importance of these two factors in the outcome of patients with severe CAP (sCAP).

A secondary analysis in a multicenter observational study was conducted in 457 patients with CAP admitted to the ICU. Patients were divided into four groups: (group-RB) those with rapid radiographic spread of pulmonary infiltrates and bacteremia (n=48), (group-R) those with rapid radiographic spread but no bacteremia (n=183), (group-B) bacteremia but without rapid radiographic spread (n=39), and (group-C) neither rapid radiographic spread nor bacteremia (n=187).

Logistic regression analysis showed that group-RB and group-R had a greater risk of developing shock than group-C (adjusted odds ratio [aOR]: 8.9, 95% confidence interval [CI]: 4.0-19.7 and aOR: 3.8, 95% CI: 2.5-5.9, respectively), while patients in group-B had no increased risk. In addition, compared to group-C, group-RB and group-R had an increased risk of ICU death (aOR: 3.4, 95% CI: 1.4-8.1 and aOR: 3.1, 95% CI: 1.7-5.7, respectively), while patients in group-B had none.

In this cohort of patients with severe CAP, radiological progression of pulmonary infiltrates in the first 48 hours is a significant adverse prognostic feature. In contrast, bacteremia does not affect outcomes.

Secondary to clinical outcome, health-related quality of life (QOL) after resection of NSCLC is of particular interest. However, few studies have explored QOL following lung resection.

Between January 1998 and December 2004, a total of 159 patients with NSCLC underwent surgical resection and were enrolled in this prospective study. QOL and clinical data were assessed prior to resection and for up to 24 months after surgery by applying the EORTC QLQ C-30 questionnaire and the lung-specific questionnaire, QLQ-LC13. QOL was calculated and the QOL following bi-/lobectomy was compared with QOL after pneumonectomy.

Overall, the 5 year survival rate was 42%. Mean survival of the pneumonectomy group was slightly lower than that of the bi-/lobectomy group, although the difference was not statistically significant (p=0.058). The rate of complications was not significantly different between the two groups. After a postoperative drop, most QOL indicators remained near baseline for up to 24 months, with the exception of physical function (p<0.001), pain (p=0.034), and dyspnoea (p<0.001), which remained significantly impaired. QOL was significantly better (difference >10 points) after bi-/lobectomy than after pneumonectomy. However, differences were statistically significant only with regards to physical function (at 3 months), social function (at 3 and 6 months), role function (at 3, 6 and 12 months), global health (at 3 and 6 months), and pain (at 6 months).

Patients who underwent lung resection for NSCLC failed to make a complete recovery after 24 months. Patients who underwent pneumonectomy had significantly worse QOL values and a decreased tendency to recover, compared with patients who underwent bi-/lobectomy. Therefore, major lung resection has a much more serious impact on the QOL of affected patients than does major visceral surgery.

It is unclear whether race/ethnicity influences survival for acute critical illnesses. We compared hospital mortality among Asian (originating from Asia or South East Asia), Native Indian, and European descent patients admitted to ICU.

Prospective cohort study of patients admitted to three ICUs (Jan 1999 to Jan 2006) in British Columbia, Canada. Multivariable analysis evaluated hospital mortality for each ethnic group, adjusting for age, sex, APACHE II score, hospital, median income, unemployment, and education. To account for differences in case mix, multivariable analysis was also restricted to those patients admitted for the five most common ICU admission diagnoses (sepsis, pneumonia, brain injury, COPD, and ARDS).

Of 7331 patients, 21% were Asian, 4% were Native Indian and 75% were European descent. Crude mortality was 33% for Asian, 30% for Native Indian and 28% for European descent patients. After adjusting for potential confounders, Native Indian descent was not associated with an increase in mortality compared to European descent. Asian descent was associated with a significantly higher mortality (OR:1.22, 95%CI: 1.06-1.41, p=0.005). After adjusting for case mix, this difference was no longer seen. For patients admitted for COPD exacerbation, Asian descent was associated with a substantial increase in mortality (OR 4.5, 95%CI: 1.56 to 12.9, p=0.005). There were no significant differences in mortality by race/ethnicity for patients who had any of the other common admitting diagnoses.

Asian and Native Indian descent patients with acute critical illness did not have an increased mortality after adjusting for differences in case mix.

Patients with COPD are believed to have a high risk of developing a depression. However, it remains unclear whether or not there is a temporal relation between COPD and depression and if the higher risk for depression is a result of having a chronic disease, or is specific for COPD. The aim of this study is to compare the risk for a physician diagnosed depression in patients with COPD, patients with diabetes mellitus (DM), and controls without chronic conditions.

The study was a prospective cohort study based on the Continuous Morbidity Registration database. Cox's proportional hazards analysis was used to identify the risk of a first episode of depression in patients with COPD compared to patients with DM and matched controls without chronic conditions. The following covariates were added to the model: age, the general practice the patient was listed with, socio-economic status, comorbidity, and gender. All patients with a diagnosis of depression preceding the date of first diagnosis of COPD or DM (dummy date in controls) were excluded.

The hazard ratios (HR) for a first episode of depression in the COPD group compared to the DM group and "healthy controls" were HR=1.80 (95%CI 1.16 - 2.81) and HR=1.68 (95%CI 1.20 – 2.35), respectively.

We found a temporal relation between COPD and physician diagnosed depression. Patients with COPD are more likely to be diagnosed with depression than patients with DM and controls without chronic conditions.

To systematically review all published case reports and the United States Food and Drug Administration's Adverse Event Reporting (FDA-AER) database to examine the relationship between statins and interstitial lung disease (ILD).

Pub Med (1987-September 2007) and the FDA–AER database (as of June 2007) were searched for reports of ILD in which a statin was listed as a causative suspect.

Two authors (one author for Pub Med cases and one for FDA–AER cases) independently abstracted patient data. Given the paucity of information, all case reports and case series in English and French were included. All adverse event reports from the FDA–AER database where a statin was listed as causative suspect were included.

The literature search using Pub Med yielded 8 articles describing a total of 14 case reports of ILD in association with statin use. The FDA–AER system database contained 162 cases of reported statin-induced ILD, as of June 2007. For every 10,000 reports of a statin-associated adverse event, approximately 1 to 40 reports were for an ILD.

Statin-induced interstitial lung disease is a possible newly recognized side effect of statin therapy. The mechanism of lung injury is not defined. The current review provides novel information from the FDA-AER that supports a possible, although unusual, pulmonary class effect of statins.

To compare the pressure characteristics of mechanical ventilation and their impact on pediatric patients with severe ARDS in the pre-PLS and post-PLS eras. Methods: The medical records of 33 patients admitted to our PICU with ARDS during the years 1992 through 1994 (pre-PLS) and 52 patients with ARDS admitted during years 2000 through 2003 (post-PLS) were retrospectively reviewed. Results: Patients' age and gender distribution was identical in both eras. Fifty-five percent of the patients in the pre-PLS era developed pneumothorax compared to 17% in the post-PLS era (p<0.05). The overall mortality rates for pre-PLS and post-PLS eras were 42% and 25%, respectively (p=0.09; NS). The mean duration of exposure to PIP values greater than 40 cm H2O was significantly longer in the pre-PLS era than in the post-LPS era. Pre-PLS patients with pneumothorax received mean maximum PIP of 72 ± 17, mean maximum PEEP of 20 ± 5 and mean maximum MAP of 46 ± 8, while patients in the post-PLS required 42 ± 2, 14 ± 2 and 30 ± 6, respectively (p<0.05 for all pressure parameters). There were no significant differences in the mechanical ventilation pressure characteristics among patients who did not develop pneumothorax during their course of management in both eras Conclusions: A significantly more aggressive use of ventilator pressure characteristics distinguished our pre-PLS era from post-PLS era and was found to be associated with a markedly higher incidence of pneumothorax. Outcome in both eras did not significantly differ, presumably due to insufficient statistical power.

In the general population, rates of certain respiratory infections (and mortality from these infections) are higher in winter. We hypothesized that, in patients with idiopathic pulmonary fibrosis (IPF) and/or pulmonary fibrosis from any cause, death rates would be increased during the winter season, independent of recognized infection. Our objective was to determine if mortality rates from IPF and/or pulmonary fibrosis of any cause exhibit seasonal variation.

Using death records from the National Center for Health Statistics, we calculated monthly mortality rates for persons with pulmonary fibrosis and developed a multivariable model to determine if these mortality rates exhibited seasonal variation.

From spring of 1992 to fall of 2003, there were 27,367,580 deaths in the United States and 170,984 decedents with pulmonary fibrosis. The average mortality rate among all persons with pulmonary fibrosis was 17.1% higher in winter (p < 0.0001), 12.7% higher in spring (p < 0.0001), and 5.2% higher in fall (p = 0.0002) than in summer months. These findings persisted when records with a diagnostic code for pneumonia were excluded from the analysis as well as when only records in which pulmonary fibrosis was the underlying cause-of-death were included in the analysis.

Mortality rates from pulmonary fibrosis exhibit significant seasonal variation, with the highest rates occurring in the winter – even when recognized infection is excluded. Further studies are necessary to determine if this seasonal variation exists in a prospective cohort – and, if so, to uncover its etiology.

Enrolling critically ill patients in clinical trials is challenging. We observed that eligible patients at San Francisco General Hospital (SFGH), a public hospital that cares largely for indigent patients, were less likely to be enrolled in a clinical trial of acute lung injury (ALI) than eligible patients at the University of California, San Francisco (UCSF), a university referral center. We examined the reasons for non-enrollment and the impact of the availability of a surrogate decision maker on critical care clinical trials enrollment.

Data collected from the Acute Respiratory Distress Syndrome (ARDS) Network trial of lower versus traditional tidal volume ventilation for patients with ALI was analyzed. Patient demographics and reasons for non-enrollment were analyzed among 531 consecutively screened patients at the two hospitals, UCSF and SFGH.

At UCSF, 1% of screened patients were not enrolled because they lacked surrogates, whereas 18% of screened patients were not enrolled at SFGH because they lacked surrogates. Lack of surrogate was the most common reason for non-enrollment among eligible patients at SFGH.

Critically ill patients with ALI at a public hospital were less likely to be enrolled in a clinical trial than patients at a university hospital, primarily because they lacked surrogates. Lack of a surrogate also was a major factor in non-enrollment in other ARDS Network hospitals. In order to provide all affected patients an opportunity to participate in research, innovative strategies for increasing enrollment in critical care research without compromising protection from research risks are needed.

To comprehensively evaluate the ability and reliability of the representative previously proposed oxyhemoglobin indices derived automatically for predicting the severity of obstructive sleep apnea hypopnea syndrome (OSAHS).

Patients with a diagnosis of OSAHS by standard polysomnography were recruited from China Medical University Hospital Centre. There were 257 patients in the learning set and 279 patients in the validation set. The presence of OSAHS was defined as AHI >5/h (Apnea Hypopnea Index). Three kinds of oxyhemoglobin indices, including the oxyhemoglobin desaturation index (ODI), time domain, and frequency domain indices were used. The degrees of severity were AHI >15/h and AHI >30/h, representing moderate and severe OSAHS. A total of 28 oxyhemoglobin indices were tested in our study.

Among the three kinds of indices, ODI had a better diagnostic performance than the time domain and frequency domain indices with the results coincident in the validation set and learning set. For predicting the severity of OSAHS with AHI > 15/h or 30/h, the ODI clinically had the higher correlation with AHI than time domain and frequency domain indices, with sensitivity/specificity achieving 84.0%/84.3% in AHI > 15/h and 87.8%/96.6% in AHI > 30/h, respectively.

Based on the smaller standard error of estimate (SEE) of the AHI, the ODI had a significantly smaller SEE than the time domain and frequency domain indices. The ODI index provided a high level of diagnostic sensitivity and specificity at different degrees of OSAHS severity.

Severe asthma subjects have increased physiologically measured air trapping. However, a similar study using CT measures of air trapping has not been performed.

This study was designed to address two hypotheses: 1) air trapping, measured by multi-detector CT quantitative methodology, would be a predictor of a more severe asthma phenotype; and 2) historical, clinical, allergic, or inflammatory risk factors could be identified via multivariate analysis.

Multi-detector CT scanning of a subset of the Severe Asthma Research Program subjects was performed at functional residual capacity. Air trapping was defined as 9.66% or more of the lung tissue less than -850 HU. Subjects who were defined as air trappers were then compared to non-trappers on clinical and demographic factors using both univariate and multivariate statistical analysis.

Air trappers were significantly more likely to have a history of asthma-related hospitalizations, ICU visits and/or mechanical ventilation. Duration of asthma (OR 1.42, 95% CI 1.08-1.87), history of pneumonia (OR 8.55, 95% CI 2.07-35.26), high levels of airway neutrophils (OR 8.67, 95% CI 2.05-36.57), air flow obstruction (FEV₁/FVC) (OR 1.61, 95% CI 1.21-2.14) and atopy (OR 11.54, 95% CI 1.97-67.70), were identified as independent risk factors associated with the air trapping phenotype.

Quantitative CT determined air trapping in asthmatic subjects identifies a group of individuals with a high risk of severe disease. Several independent risk factors for the presence of this phenotype were identified, perhaps most interestingly history of pneumonia, neutrophilic inflammation, and atopy.