In 32 patients, serum cholesterol, triglycerides, high-density lipoprotein cholesterol, fibrinogen, apolipoprotein A-I, apolipoprotein B (ApoB), high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor (TNF)-, leptin, malondialdehyde (MDA), and erythrocytic glutathione peroxidase (GPx) activity were measured at baseline and after 8 weeks of CPAP. The insulin resistance index (homeostasis model assessment [HOMA-IR]) was based on the homeostasis model assessment method, the CVD risk was calculated using the multivariable risk factor algorithm.

In patients who used CPAP for ≥ 4 h/night (n = 16), CPAP therapy reduced systolic BP and diastolic BP (p = 0.001 and p = 0.006, respectively), total cholesterol (p = 0.002), ApoB (p = 0.009), HOMA-IR (p = 0.031), MDA (p = 0.004), and TNF- (p = 0.037), and increased erythrocytic GPx activity (p = 0.015), in association with reductions in the global CVD risk (from 18.8 ± 9.8 to 13.9 ± 9.7%, p = 0.001). No significant changes were seen in patients who used CPAP for < 4 h/night. Mask leak was the strongest predictor of compliance with CPAP therapy.

In patients with severe OSA and metabolic syndrome, good compliance to CPAP may improve insulin sensitivity, reduce systemic inflammation and oxidative stress, and reduce the global CVD risk.

Clinicaltrials.gov Identifier: NCT00635674.

In this cross-sectional study of 41 patients with IPF from a prospectively designed cohort, we ascertained sleep quality by means of the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale. Health status, baseline demographics, and physiologic parameters were also assessed.

Patients with IPF reported extremely poor sleep quality and high frequency of daytime sleepiness, which differs significantly from normal control populations. Further, poor sleep quality was not associated with body mass index, age, gender, or lung function. This population also demonstrated extremely poor health status in a number of domains, including physical function and vitality. Poor sleep quality (by the global PSQI) was significantly associated with decreased quality of life (QOL) in several domains, including role of physical function (r = – 0.58, p = 0.001), vitality (r = – 0.43, p = 0.015), and role of emotions (r = – 0.40, p = 0.023).

Poor sleep quality is extremely common in patients with IPF and is not predicted by variables traditionally associated with sleep-disordered breathing. Further, poor sleep quality is associated with poor QOL. These findings suggest that systematic evaluation of the cause of poor sleep quality in IPF is merited.

This study measured airway responsiveness to methacholine by dosimeter method and tidal breathing method in 27 subjects with suspected asthma. The dosimeter was modified to deliver an identical volume to that obtained with the tidal breathing method. Concentration-response curves were characterized by the PC₂₀.

The dosimeter method PC₂₀ was significantly higher than the tidal breathing method PC₂₀, with geometric mean values of 4.03 (95% confidence interval [CI], 1.86 to 8.78 mg/mL) and 2.19 (95% CI, 1.32 to 3.64 mg/mL; p = 0.04), respectively. The mean difference in the PC₂₀ value detected with each method was similar in subjects with tidal breathing method PC₂₀ values ≥ 2 mg/mL (0.77 doubling concentrations) and in those with PC₂₀ values < 2 mg/mL (0.96 doubling concentrations; p = 0.83).

The tidal breathing method produces PC₂₀ values significantly lower than a modified dosimeter method, which delivers the same volume of aerosol. These results suggest that the discordant PC₂₀ values obtained with the two methods are not due to differences in the dose of agonist delivered to the mouth.

All subjects underwent pulmonary function testing, hydrostatic weighing, and MRI scans. Data were analyzed for the men and women separately by independent t test, and the relationships between variables were determined by regression analysis.

All body composition measurements were significantly different among the lean and obese men and women (p < 0.001). However, with only a few exceptions, fat distribution was similar among the lean and obese men and women (p > 0.05). The mean EELV was significantly lower in the obese men (39 ± 6% vs 46 ± 4% total lung capacity [TLC], respectively; p < 0.0005) and women (40 ± 4% vs 53 ± 4% TLC, respectively; p < 0.0001) compared with lean control subjects. Many estimates of body fat were significantly correlated with EELV for both men and women.

In both men and women, the decrease in EELV with obesity appears to be related to the cumulative effect of increased chest wall fat rather than to any specific regional chest wall fat distribution. Also, with only a few exceptions, relative fat distribution is markedly similar between lean and obese subjects.

We recruited 2,396 apparently healthy adults and investigated the associations among pulmonary function, metabolic abnormality, and MetS, as defined by three different criteria. Abnormal pulmonary function was evaluated by both continuous pulmonary function variables including the percentage of predicted FVC (%PFVC) and a clinical category defined according to the American Thoracic Society/European Respiratory Society guidelines.

CRP and %PFVC, but not FEV₁/FVC ratio, were significantly correlated with metabolic abnormalities even after adjustment for confounders including waist circumference. After adjustment for age, sex, and height, the odds ratios (ORs) of a restrictive pattern (RP), as defined by a reduced FVC and a normal FEV₁/FVC ratio using the lower limit of normal and RP substitutively defined by reduced FVC and an FEV₁/FVC ratio of ≥ 85% for MetS, were 1.76 to 2.52 (p < 0.05 to < 0.0001) and 1.87 to 2.28 (p < 0.05 to < 0.01), respectively. The obstructive pattern (OP) was not significantly associated with any MetS criteria. A moderate-to-severe RP, but not a high CRP level (> 3.0 mg/L), was consistently associated with the three MetS criteria (OR, 2.08 to 3.57; p < 0.05 to < 0.01), even after adjustment for confounders.

Impaired restrictive pulmonary function, but not OP, might be associated with metabolic disorders and MetS in a severity-dependent manner.

Data collected from the ARDS Network trial of lower vs traditional tidal volume ventilation for patients with ALI was analyzed. Patient demographics and reasons for nonenrollment 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 nonenrollment 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 nonenrollment 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.

We performed a pooled analysis of all five multicenter studies in which patients with ARDS due to various predisposing events were treated with rSP-C surfactant. Patients received either usual care (n = 266) or usual care plus up to four intratracheal doses (50 mg/kg) of rSP-C surfactant (n = 266). Factors influencing the study end points were analyzed using descriptive statistics, analysis of covariance, and logistic regression models.

ARDS was most often associated with pneumonia or aspiration, sepsis, and trauma or surgery. For the overall patient population, treatment with rSP-C surfactant significantly improved oxygenation (p = 0.002) but had no effect on mortality (32.6%). Multivariate analysis showed age and acute physiology and chronic health evaluation (APACHE) II score to be the strongest predictors of mortality. In the subgroup of patients with severe ARDS due to pneumonia or aspiration, surfactant treatment was associated with markedly improved oxygenation (p = 0.0008) and improved survival (p = 0.018).

rSP-C surfactant improved oxygenation in patients with ARDS irrespective of the predisposition. Post hoc evidence of reduced mortality associated with surfactant treatment was obtained in patients with severe respiratory insufficiency due to pneumonia or aspiration. Those patients are the focus of a current randomized, blinded, clinical trial with rSP-C surfactant.

Fourteen patients with mild-to-moderate persistent asthma (6 men, 8 women) were recruited. During the recruitment visit, the patients, previously treated for asthma following Global Initiative for Asthma recommendations, underwent clinical evaluation and pulmonary function tests (PFTs). Then, after 4 weeks of washout from inhaled antiinflammatory treatment, the patients underwent a basal visit performing PFTs, challenge test to methacholine, and determination of eNO and sEos counts. These procedures were repeated after 3, 6, and 12 months while the patients were treated with inhaled steroids in a stepwise fashion according to eNO and sEos values.

At the end of the study, a significant decrease in eNO and sEos was observed (57.2 ± 32.8 parts per billion [ppb] vs 22.1 ± 10.8 ppb, p < 0.01; and 27.1 ± 27.1% vs 3.7 ± 3.5%, p < 0.01, respectively). A close correlation (r² = 0.41, p < 0.01) between the percentage change of eNO and sEos was observed only after 6 months. Patients treated according to the levels of these inflammatory markers had fewer symptoms and fewer exacerbations compared to those the year before when they were conventionally treated.

Our results show the usefulness of eNO and sEos for titrating treatment in asthmatic patients in order to achieve better long-term control of the disease. The eNO decrease reflects adequately the reduction of sEos only after 6 months.

In a randomized, double-blind, crossover study, 21 patients with mild asthma inhaled ciclesonide 320 µg (ex-actuator) qd, ciclesonide 640 µg (ex-actuator) bid, and placebo for 7 days. Exhaled NO and AHR to adenosine monophosphate (AMP), measured as the provocative concentration of AMP producing a 20% reduction in FEV₁ (PC₂₀FEV₁), were assessed after inhalation on days 1, 3 and 7. Eosinophil levels in induced sputum were also measured.

Ciclesonide 320 µg qd and 640 µg bid produced significantly greater improvements in PC₂₀FEV₁ compared with placebo on day 1 (within 2.5 h), and on days 3 and 7 (all p < 0.0001). On day 3, both ciclesonide doses significantly reduced exhaled NO levels by – 17.7 parts per billion (p < 0.0001) and – 15.4 parts per billion (p < 0.003) vs placebo, respectively. Significant reductions were maintained during the study with both ciclesonide doses (p < 0.01). A nonsignificant trend towards a decrease in eosinophil cell numbers was observed after 7 days of ciclesonide treatment, especially in patients receiving the higher dose.

A single dose of ciclesonide decreased AHR to AMP and exhaled NO within 3 h, while FEV, improved at 3 days and 7 days.

ClinicalTrials.gov Study ID Number BY9010/M1-125.

We enrolled 576 stable COPD outpatients in Spain and the United States and observed them for at least 3 years (median, 60 months). We measured FEV₁, body mass index, Pao₂, Charlson comorbidity score, 6-min walk distance (6MWD), and oxygen saturation by pulse oximetry (Spo₂) during the 6MWT. Desaturation was defined as a fall in Spo₂ ≥ 4% or Spo₂ < 90%. Regression analysis helped determine the association between these variables and all-cause and respiratory mortality.

The 6MWD was a good predictor of all-cause and respiratory mortality primarily in patients with FEV₁ < 50% of predicted (p < 0.001) after adjusting for all covariates. Patients with desaturation during the 6MWT had a higher mortality rate than patients without desaturation (67% vs 38%, p < 0.001). Oxygen desaturation predicted mortality (relative risk, 2.63; 95% confidence interval, 1.53 to 4.51; p < 0.001) but with less power than Pao₂ at rest.

The 6MWD helps predict mortality primarily in patients with severe COPD. Although the oxygen desaturation profile during the 6MWT improves the predictive ability of the 6MWD, it appears to be of less relevance than in other lung diseases and than the resting Pao₂.

Twenty patients (14 men; mean age, 73.4 years [SD, 6.8 years]; FEV₁, 1.0 L [SD, 0.5 L]) with stable COPD were recruited after completing a 7-week pulmonary rehabilitation program. Patients were either hypoxic at rest or had desaturation during exercise. Patients were randomized to an 8-week, double-blind, placebo-controlled trial of cylinder oxygen vs cylinder air. Total domestic physical activity and health-related quality of life (HRQL) measures were recorded before and after intervention.

There were no significant changes in domestic activity or HRQL measures after the intervention for either cylinder oxygen or cylinder air, except for a worsening of the Chronic Respiratory Questionnaire dyspnea domain on cylinder air. There was a significant increase in mean duration (minutes per day) of cylinder use (p < 0.05) between weeks 1 vs 7 and weeks 1 vs 8 for the oxygen group. However, when comparing the two groups together, there were no between-group differences in cylinder use or time spent outside the home. Over the 8 weeks the majority of patients were using the cylinders in the home rather than outside, however, the number of times patients reported using the cylinders outside the home increased over the 8 weeks for the oxygen group.

In the short term, ambulatory oxygen therapy is not associated with improvements in physical activity, HRQL, or time spent away from home. However, the use of cylinder oxygen increased over the 8 weeks compared to cylinder air. Patients need time to learn how to use oxygen, and ambulatory oxygen appears to enhance activities rather than increase them.

National Research Register N0123109178.

A prospective cohort study of general medicine outpatients seen at one of seven Veterans Affairs (VA) medical centers who returned health screening questionnaires. Three screening questionnaires, AUDIT-C (0 to 12 points), CAGE (0 to 4 points), and a single item about the frequency of drinking six or more drinks on an occasion (binge drinking), were used to classify alcohol consumption. The main outcome, COPD exacerbation, was based on primary VA discharge diagnosis (International Classification of Diseases, Ninth Revision) or outpatient diagnosis of COPD accompanied by prescriptions for either antibiotics or prednisone within 2 days.

Among the 30,503 patients followed up for a median of 3.35 years, those patients with AUDIT-C scores ≥ 6, CAGE scores ≥ 2, or who reported binge drinking at least weekly were at an increased risk of COPD exacerbation in age-adjusted analysis. Adjusted hazard ratios were 1.4 (95% confidence interval [CI], 1.1 to 1.7) for AUDIT-C score ≥ 6, 1.4 (95% CI, 1.3 to 1.5) for CAGE score ≥ 2, and 1.6 (95% CI, 1.2 to 2.2) for those who reported binge drinking daily or almost daily. However, with adjustment for measures of tobacco use, the association between alcohol consumption and increased risk of COPD exacerbation was no longer evident.

Alcohol consumption, whether quantified by AUDIT-C, CAGE score, or binge drinking, was not associated with an increased risk of COPD exacerbation independent of tobacco use.

Clinical records of 172 consecutive children aged ≤ 3 months were reviewed. PMV was defined as mechanical ventilation (MV) ≥ 72 h following operation. After univariate analysis, a stepwise logistic regression analysis was used to evaluate the independent risk factors for PMV following cardiac surgery. The predictive ability of risk factors for PMV was assessed using an area under the receiver operating characteristic (ROC) curve.

Sixty-one patients required PMV after cardiac surgery. The median duration of MV was 150 h in PMV patients, while it was 28 h in non-PMV patients. The independent risk factors for PMV were risk adjustment for surgery for congenital heart disease (RACHS)-1 (p = 0.041), nosocomial pneumonia (p = 0.001), low cardiac output syndrome (LCOS) [p = 0.001], postoperative cumulative positive fluid balance (p = 0.032), and extubation failure (EF) [p = 0.027]. The value for the ROC curve was 0.940.

The present results strongly suggest that RACHS-1, nosocomial pneumonia, LCOS, fluid retention postoperatively, and EF are risk factors for PMV in neonates and young infants undergoing reparative surgery for congenital heart disease.

The present study was a prospective, international, multicenter, randomized, open-label extension of the Sitaxsentan To Relieve Impaired Exercise-2 trial. All-cause mortality, time to discontinuation (all causes) from monotherapy, time to discontinuation due to adverse events, time to elevations in and time to discontinuation due to elevated hepatic transaminases, and time to first clinical worsening event were evaluated. Patients initially receiving sitaxsentan at 50 mg were excluded from the main analysis. The distributions of time-to-event variables are estimated using Kaplan-Meier methods, and treatment effects are evaluated using the Cox proportional hazards model.

Patients treated with sitaxsentan at 100 mg had 96% overall survival and a 34% risk for a clinical worsening event by 1 year. In addition, there was a 6% risk of elevated aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels > 3 x upper limit of normal range (ULN) at 1 year and a 15% risk of discontinuation due to adverse events. Patients treated with bosentan had 88% overall survival and a 40% risk of a clinical worsening event by 1 year. In addition, there was a 14% risk for elevated AST and/or ALT levels > 3 x ULN at 1 year and a 30% risk of discontinuation due to adverse events.

At 1 year, sitaxsentan therapy appears safe and efficacious for patients with PAH; reductions in mortality and the risk for clinical worsening events provide support for durability of efficacy.

We have studied the expression levels of ILT-4 both in vitro in cancer cell lines and in vivo in tumor tissues from 70 patients with non-small cell lung cancer (NSCLC) by reverse transcriptase-polymerase chain reaction, fluorescence-activated cell sorting, and immunohistochemical analysis.

Three cancer cell lines (H1299, A549, and U1810) express ILT-4 messenger RNA, and only two cell lines (H1299 and A549) express ILT-4 protein on the cell surface. Approximately 37.1% of 70 tumor tissue samples express ILT-4, which is localized in the cell membrane and cytoplasm. In addition, tumor cells and stromal and plasma cells also express ILT-4. The number of infiltrating lymphoid cells in the tumor tissues that express B7-H3 was much lower than those that did not, but there is no significant correlation between ILT-4 expression and disease progression including nodal metastasis.

These findings suggest that ILT-4 is frequently expressed in both tumor and stromal cells of NSCLC, and it might play an important role in regulation of the host immune system.

We used data collected in 1,722 consecutive patients with clinically suspected PE to analyze the 3-month venous thromboembolism (VTE) rate in all patients with a normal d-dimer concentration and separately for patients who have a normal d-dimer concentration with an unlikely or likely clinical probability for PE, as assessed by the Wells clinical decision rule.

The 3-month VTE rate in all patients with a normal d-dimer concentration (n = 563) was 2.3% (95% confidence interval [CI], 1.4 to 3.9%). In the patients with an unlikely probability of PE (n = 477), VTE was confirmed in 1.1% of the patients with a normal d-dimer concentration (95% CI, 0.4 to 2.4%). In those patients with a likely clinical probability of PE (n = 86), VTE was confirmed in 9.3% of the patients with a normal d-dimer concentration (95% CI, 4.8 to 17.3%). The difference in VTE incidence between patients with unlikely and likely clinical probabilities of PE was significant (p < 0.001).

Our findings indicate that it is of utmost importance to first examine the patient and assess the clinical probability, after which the d-dimer concentration can be taken into account, in order to prevent physicians from being influenced by a normal d-dimer test result when they evaluate the clinical probability of PE. Patients with a likely clinical probability should undergo further testing, regardless of the d-dimer test outcome.

Participants received placebo or alendronate, 70 mg once weekly, for 12 months. All participants received 800 IU of vitamin D and 1,000 mg of calcium daily. Adults with confirmed CF with a bone mineral density (BMD) T score of < – 1.0 were eligible for inclusion. Participants who had undergone organ transplantation or had other reported contraindications were excluded from the study. The primary outcome measure was the mean (± SD) percentage change in lumbar spine BMD after 12 months. Secondary measures included the percentage change in total hip BMD, the number of new vertebral fractures (grade 1 or 2), and changes in quality of life.

A total of 56 participants were enrolled in the study (mean age, 29.1 ± 8.78 years; 61% male). The absolute percentage changes in lumbar spine and total hip BMDs at follow-up were significantly higher in the alendronate therapy group (5.20 ± 3.67% and 2.14 ± 3.32%, respectively) than those in the control group (– 0.08 ± 3.93% and – 1.3 ± 2.70%, respectively; p < 0.001). At follow-up, two participants (both in the control group) had a new vertebral fracture (not significant), and there were no differences in quality of life or the number of adverse events (including serious and GI-related events).

Alendronate therapy was well tolerated and produced a significantly greater increase in BMD over 12 months compared with placebo.

ClinicalTrials.gov Identifier: NCT00157690

To evaluate the effect of surgical tracheobronchoplasty on symptoms, functional status, quality of life, lung function, and exercise capacity in patients with severe and symptomatic TBM.

A prospective observational study in which baseline measurements were compared to those obtained 3 months after surgical tracheobronchoplasty.

Of 104 referred patients to our complex airway center for severe TBM, 77 had baseline measurements. Of this group, 57 patients had severe malacia and underwent stent placement for central airway stabilization. Of those, 37 patients reported improvement in respiratory symptoms and 35 were considered for surgical tracheobronchoplasty. Two patients were excluded from surgery for medical reasons. Median age was 61 years (range, 39 to 83 years), 20 patients were men, 11 patients (31%) had COPD, 9 patients (26%) had asthma, and 4 patients (11%) had Mounier-Kuhn syndrome. Thirty-three patients (94%) presented with severe dyspnea, 26 patients (74%) with uncontrollable cough, and 18 patients (51%) reported recurrent pulmonary infections. Two patients (3%) presented with respiratory failure requiring mechanical ventilation. After surgery, quality of life scores improved in 25 of 31 patients (p < 0.0001), dyspnea scores improved in 19 of 26 patients (p = 0.007), functional status scores improved in 20 of 31 patients (p = 0.003), and mean exercise capacity improved in 10 patients (p = 0.012).

In experienced hands, surgical central airway stabilization with posterior tracheobronchial splinting using a polypropylene mesh improves respiratory symptoms, health-related quality of life, and functional status in highly selected patients with severe symptomatic TBM.

Clinicaltrials.gov Identifier: NCT00550602

PubMed (1987 to 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 in which a statin was listed as causative suspect were included.

The literature search using PubMed yielded eight 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 ILD.

Statin-induced ILD 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.

We retrospectively reviewed our clinical experience at National Jewish Medical and Research Center for patients with surgical lung biopsy-proven fibrotic HP who had an acute decline in respiratory status and met criteria similar to those proposed for the diagnosis of an AE of IPF.

Over a 2-year period, we identified four patients with an AE of fibrotic HP. All patients had a clinical course similar to that most frequently described in AEs of IPF: respiratory failure requiring assisted ventilation, lack of clinical response to high-dose corticosteroid therapy, and a poor prognosis (all cases resulted in death or emergent lung transplantation). Lung biopsy at the time of the AE, explant, or autopsy revealed organizing diffuse alveolar damage superimposed on fibrotic lung disease.

Fibrotic HP, like other forms of fibrotic lung disease, can be associated with AEs of disease. Further investigation into similarities and pathways common in AEs of various fibrotic lung diseases may yield additional insight into this recently recognized syndrome.