Methods: The authors conducted a systematic review with metaanalysis of randomized clinical trials (≥ 1 month in duration) in the published literature that have compared LABAs with placebo or anticholinergics in stable poorly reversible and reversible COPD.

Results: MEDLINE, EMBASE, CINAHL, and the Cochrane Controlled Trials Register were searched to identify 27 studies. LABAs reduced severe exacerbations compared with placebo (relative risk [RR], 0.78; 95% confidence interval [CI], 0.67 to 0.91). There was no significant difference between LABA and placebo groups in terms of respiratory deaths (RR, 1.09; 95% CI, 0.45 to 2.64). Use of LABAs with inhaled corticosteroids reduced the risk of respiratory death compared with LABAs alone (RR, 0.35; 95% CI, 0.14 to 0.93). Patients receiving LABAs showed significant benefits in airflow limitation measures, health-related quality of life, and use of rescue medication. Finally, tiotropium decreased the incidence of severe COPD exacerbations compared with LABAs (RR, 0.52; 95% CI, 0.31 to 0.87).

Conclusion: This review supports the beneficial effects of the use of LABAs in patients with stable moderate-to-severe COPD, and did not confirm previous data about an increased risk for respiratory deaths. Also, our analysis suggests the superiority of tiotropium over LABAs for the treatment of stable COPD patients.

Methods: B-type natriuretic peptide (BNP), a quantitative marker of cardiac stress, was determined in 208 consecutive patients presenting to the emergency department with an acute exacerbation of COPD (AECOPD). The accuracy of BNP to predict death at a 2-year follow-up was evaluated as the primary end point. The need for intensive care and in-hospital mortality were determined as secondary end points.

Results: BNP levels were significantly elevated during the acute exacerbation compared to recovery (65 pg/mL; interquartile range [IQR], 34 to 189 pg/mL; vs 45 pg/mL; IQR, 25 to 85 pg/mL; p < 0.001), particularly in those patients requiring ICU treatment (105 pg/mL; IQR, 66 to 553 pg/mL; vs 60 pg/mL; IQR, 31 to 169 pg/mL; p = 0.007). In multivariate Cox regression analysis, BNP accurately predicted the need for ICU care (hazard ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.24 for an increase in BNP of 100 pg/mL; p = 0.008). In a receiver operating characteristic analysis to evaluate the potential of BNP levels to predict short-term and long-term mortality rates, areas under the curve were 0.55 (SD, 0.71; 95% CI, 0.41 to 0.68) and 0.56 (SD, 0.53; 95% CI, 0.45 to 0.66, respectively).

Conclusions: In patients with AECOPD, BNP levels independently predict the need for intensive care. However, BNP levels failed to adequately predict short-term and long-term mortality rates in AECOPD patients.

Study objective: The goal of this study was to determine if the phenotype PiMZ is associated with an accelerated decline in diffusing capacity of the lung for carbon monoxide (Dlco).

Design and methods: The Tucson Epidemiologic Study of Airway Obstructive Disease is a prospective, population-based cohort study initiated in 1972. Participants completed standardized questionnaires in up to 12 periodic surveys and Dlco assessments in up to 4 surveys. Random-effects models were used to determine the effects of ₁-antitrypsin phenotypes on percentage of predicted (% predicted) Dlco levels among 1,075 subjects ≥ 18 years old.

Results: % predicted Dlco declined more rapidly in subjects who smoked compared to nonsmoking subjects. Additionally, in smokers, the PiMZ phenotype was associated with borderline % predicted Dlco deficits at age 40 years (8.6%; p = 0.075) and significant % predicted Dlco deficits at age 60 years (15.2%; p = 0.001) and 80 years (21.9%; p = 0.003), as compared with the PiMM phenotype.

Conclusions: Dlco may be a more sensitive indicator of the long-term effects of intermediate levels of ₁-antitrypsin on lung function especially in subjects who smoke.

Methods: Levels of MMP and tissue inhibitors of metalloproteinase in BAL fluid and their expression on lung tissues were compared between normal control subjects (n = 5) and the patients with IPF (n = 6) and COP (n = 11).

Results: There was no significant difference in BAL fluid MMP-7 levels between UIP and COP, although it was higher in both diseases compared to normal control subjects. Furthermore, the pattern and the degree of MMP-7 expression in lung tissues were also similar in both IPF and COP, whereas MMP-2 level was higher in COP and MMP-9 level was higher in IPF.

Conclusion: MMP-7 seems to play an important role in the pathogenesis of not only IPF but also COP; therefore, it may not be the key factor determining the prognosis or reversibility of IIPs.

Methods: We asked 190 intensivists from 34 ICUs in the area of Paris, France, to anonymously complete a 29-item questionnaire about their opinions regarding the ordering of CXRs; each item described a clinical scenario. Of the 29 scenarios, 10 dealt with the placement of medical devices, 8 with the presence of medical devices, and 11 with other clinical situations. The study was based on a Delphi process deployed over the Internet through an original software application. Three Delphi rounds were run between January and March 2006, using the same questionnaire. Detailed feedback for the answers given during the previous round was supplied to each intensivist solicited for updating his answers.

Results: Eighty-two intensivists from 32 ICUs completed the study. A consensus emerged that routine CXRs were necessary for eight scenarios and unnecessary for two scenarios. The study also shed light on items without a consensus. In particular, 75% of intensivists (58% on the first round) did not support obtaining daily routine CXRs in intubated patients.

Conclusion: The study underlines situations in which intensivists do not support the guidelines and outlines recommendations likely to be followed in clinical practice.

Purpose: To describe the clinical course and outcome of patients with ILD and acute respiratory failure in relation to ventilatory parameters.

Methods: We retrospectively identified a cohort of ventilated patients with ILD who had been admitted to five ICUs at a single institution. We analyzed demographic data, pulmonary function test results, severity of illness, and the parameters of continuous ventilation for the initial 24 h after admission to the ICU. Primary outcomes were survival to hospital discharge and 1-year survival.

Main results: Of 94 patients with ILD, 44 (47%) survived to hospital discharge and 39 (41%) were alive at 1 year. Nonsurvivors were less likely to be postoperative, had higher severity of illness, and were ventilated at higher airway pressures and lower tidal volumes. Step changes in positive end-expiratory pressure (PEEP) of > 10 cm H₂O were attempted in 20 patients and resulted in an increase in plateau pressure (median difference, + 16 cm H₂O; interquartile range [IQR], 9 to 24 cm H₂O) and a decrease in respiratory system compliance (median difference, – 0.28 mL/kg/cm H₂O; IQR, – 0.43 to – 0.13 mL/kg/cm H₂O). The Cox proportional hazards model revealed that high PEEP (hazard ratio, 4.72; 95% confidence interval [CI], 2.06 to 11.15), acute physiology and chronic health evaluation (APACHE) III score predicted mortality (hazard ratio 1.33; 95% CI, 1.18 to 1.50), age (hazard ratio, 1.03; 95% CI, 1 to 1.05), and low Pao₂/fraction of inspired oxygen ratio (hazard ratio, 0.96; 95% CI, 0.92 to 0.99) to be independent determinants of survival.

Conclusion: Both severity of illness and high PEEP settings are associated with the decreased survival of patients with ILD who are receiving mechanical ventilation.

Methods: We used the Medline database to select studies with the key words "acute lung injury," "ARDS," "acute respiratory failure," and "mechanical ventilation." All studies that reported mortality rates for patients with ALI/ARDS defined according to the criteria of the American European Consensus Conference were selected. We excluded studies with < 30 patients and studies limited to specific subgroups of ARDS patients such as sepsis, trauma, burns, or transfusion-related ARDS.

Results: Seventy-two studies were included in the analysis. There was a wide variation in mortality rates among the studies (15 to 72%). The overall pooled mortality rate for all studies was 43% (95% confidence interval, 40 to 46%). Metaregression analysis suggested a significant decrease in overall mortality rates of approximately 1.1%/yr over the period analyzed (1994 to 2006). The mortality reduction was also observed for hospital but not for ICU or 28-day mortality rates.

Conclusions: In this literature review, the data are consistent with a reduction in mortality rates in general populations of patients with ALI/ARDS over the last 10 years.

Methods: This study was performed at a tertiary care hospital. Home nocturnal oximetry was performed on elective surgical patients with clinical features of OSA. The number of episodes per hour of oxygen desaturation (or oxygen desaturation index) of ≥ 4% (ODI4%) was determined. Subjects with five or more desaturations per hour (ODI4%≥ 5) were compared to those with less than five desaturations per hour (ODI4%< 5). Hospital records were reviewed to assess the incidence and type of postoperative complications.

Results: A total of 172 patients were investigated as part of this study. No significant differences were observed between groups in terms of age, body mass index, number of medical comorbidities, or smoking history. Patients with an ODI4%≥ 5 had a significantly higher rate of postoperative complications than those with ODI4%< 5 (15.3% vs 2.7%, respectively [p < 0.01]; adjusted odds ratio, 7.2; 95% confidence interval, 1.5 to 33.3 [p = 0.012]). The complication rate also increased with increasing ODI severity (patients with an ODI4% of 5 to 15 events per hour, 13.8%; patients with an ODI4% of ≥ 15 events per hour, 17.5%; p = 0.01) Complications were respiratory (nine patients), cardiovascular (five patients), GI (one patient), and bleeding (two patients). The hospital length of stay was similar in both groups.

Conclusion: An ODI4%≥ 5, determined by home nocturnal oximetry, in patients with clinical features of OSA is associated with an increased rate of postoperative complications.

Methods: We retrospectively studied patients seen in a dental sleep clinic between 2002 and 2006. Patients selected for OA treatment underwent baseline polysomnography, were individually fit with an OA, and were instructed to titrate it at home until symptom resolution or discomfort. During follow-up polysomnography, additional titration was performed as needed. Primary outcome was successful treatment, defined as apnea-hypopnea index (AHI) <10 events per hour and AHI decrease at least 50% from baseline. Logistic regression models were created to identify associations between patient characteristics and successful treatment. Overall differences in AHI at baseline, after home titration, and after final titration were compared using Kruskal-Wallis test, and post hoc comparisons were performed with sign tests, with Bonferroni corrections.

Results: Of 57 subjects treated with an OA, 37 subjects (64.9%) were successfully treated with OA therapy. Of the 49 subjects for whom data were available for AHI after home titration, 27 subjects (55%) achieved successful treatment of OSA by self-titration, without need for further titration during follow-up polysomnography.

Conclusions: A majority of subjects, regardless of OSA severity, are successfully treated with an OA. Men and younger patients were found to be the best responders. The titration protocol for an OA offers a beneficial initial step in the treatment of OSA.

Methods: Patient-reported depressive symptoms were obtained using the Geriatric Depression Scale (GDS) [possible score 0 to 30; higher score indicates more depressive symptoms]. Patients were categorized as having a physician-reported depressive disorder if they had the following: a diagnosis of depression, depressive symptoms described in medical charts, or were prescribed antidepressants at doses used to treat depression. Patients also completed the Severity of Asthma Scale (SOA) [possible score 0 to 28; higher score indicates more severe] and the Asthma Control Questionnaire (ACQ) [possible score 0 to 6; higher score indicates worse control].

Results: Two hundred fifty-seven patients were included in this analysis (mean age, 42 years; 75% women). Mean SOA and ACQ (± SD) scores were 5.9 ± 4.2 and 1.4 ± 1.2, respectively; and mean GDS score was 6.3 ± 6.4. After adjusting for age, sex, race, Latino ethnicity, education, medication adherence, body mass index, and smoking status, patient-reported depressive symptoms were associated with asthma severity (p = 0.007) and with asthma control (p = 0.0007). In contrast, physician-reported depressive disorders were associated with asthma severity (p = 0.04) but not with asthma control (p = 0.22) after adjusting for covariates.

Conclusions: Physician- and patient-reported depressive conditions were associated with asthma severity. In contrast, patient-reported depressive symptoms were more closely associated with asthma control than were physician-reported depressive disorders. Identifying associations between depressive conditions and asthma severity and control is necessary to concurrently treat these conditions in this population.

Trial registration: Clinicaltrials.gov Identifier: NCT00195117.

Methods: Simultaneous single-breath measurements of Dlco and Dlno were performed in 10 patients with cystic fibrosis (CF) [mean ± SD age, 33 ± 9 years; FEV₁, 69 ± 28% of predicted] and 10 healthy subjects (age, 31 ± 9 years; FEV₁, 108 ± 8% of predicted), using the Masterscreen PFT (Viasys/Jaeger; Höchberg, Germany), with 45 ppm of inspired nitric oxide (NO), and breath-hold times of 4 s, 6 s, 8 s, and 10 s. The last two of three consecutive measurements were used for analysis.

Results: In healthy subjects but not patients with CF, Dlno, and Dlco differed significantly (p < 0.05 each) between breath-hold times. Differences primarily occurred at 4 s and 10 s, while at 6 s and 8 s alveolar volume (VA), Dlno, Dlco, and Dlno/Dlco were similar. Variability of consecutive measurements (either three or the last two measurements) did not depend on breath-hold time. At 8 s, mean variabilities of Dlno and Dlco in healthy subjects were 4.9% and 2.5%, respectively, and 4.2% and 3.2% at 6 s. At 8 s, mean variabilities of Dlno and Dlco in CF patients were 4.4% and 1.9%, and 7.4% and 3.3% at 6 s.

Conclusions: Single-breath determinations of dlno and dlco showed no difference between breath-hold times of 6 s and 8 s in subjects with or without airway obstruction, and reproducibility was acceptable. Standardization of breath-hold time for Dlno measurements seems important for clinical and research comparisons.

Methods: In a prospective, randomized, cross-over study, 27 COPD subjects (FEV₁, 38 ± 14% [mean ± SD]; 15 men) attended three separate test sessions, completing six 6MWTs. To familiarize all subjects with both tracks, the first two sessions comprised two 6MWTs on either a circular or straight track. During the final session, each subject was tested once on the straight and once on the circular track.

Results: The distance walked on the circular track exceeded the straight track by 13 ± 17 m (p < 0.001). The limit of agreement between tracks was 33 m. Coefficient of repeatability values when the test was completed on different days for the straight and circular tracks were 51 m and 65 m, respectively.

Conclusions: When evaluating changes in 6-min walk distance in groups of patients, track layout should be standardized. However, the effect of modifying track layout on an individual’s walking distance is small compared to their daily variability in walk distance. Therefore, standardizing track layout for any given individual may be inconsequential when evaluating the change in distances from tests performed on different days.

Methods: Ex-preterm (gestation ≤ 35 completed weeks) infants ready for air transfer from the intensive/special care nursery to regional hospitals were studied. A pretransfer HCT was performed by exposing infants to 14% oxygen for 20 min. Failure was defined as a sustained fall in pulse oxygen saturation (Spo₂) ≤ 85%. A nurse blinded to the test result monitored the in-flight oxygen saturations in each infant. If Spo₂ fell to ≤ 85%, oxygen was administered.

Results: Forty-six infants with median gestation of 32.2 weeks (range, 24 to 35.6 weeks) and birth weight of 1,667 g (range, 655 to 2,815 g) were recruited. No infants were receiving supplemental oxygen at the time of transfer. The HCT was performed at a median corrected age of 35.8 weeks (range, 33.1 to 43 weeks). Thirty-five infants (76%) passed the test, and the remainder failed. During the flight, 16 infants met the criteria for in-flight oxygen, but 12 of these infants (75%) had passed the preflight HCT. Of the 11 infants who failed the HCT, only 4 infants (36%) required in-flight oxygen. The HCT incorrectly predicted in-flight responses in 42% (19 of 46 infants).

Conclusions: A significant percentage of ex-preterm neonates require in-flight oxygen supplementation. The HCT is not accurate for identifying which infants are at risk for in-flight hypoxia.

Methods: We reviewed the records of consecutive patients in whom non-small cell lung cancer (NSCLC) had been diagnosed between January 1, 2002, and December 31, 2003, at the Veterans Affairs Palo Alto Health Care System. We used multivariable statistical methods to identify independent predictors of timely care and examined the effect of timeliness on survival.

Results: We identified 129 veterans with NSCLC (mean age, 67 years; 98% men; 83% white), most of whom had adenocarcinoma (51%) or squamous cell carcinoma (30%). A minority of patients (18%) presented with a solitary pulmonary nodule (SPN). The median time from the initial suspicion of cancer to treatment was 84 days (interquartile range, 38 to 153 days). Independent predictors of treatment within 84 days included hospitalization within 7 days (odds ratio [OR], 8.2; 95% confidence interval [CI], 2.9 to 23), tumor size of > 3.0 cm (OR, 4.8; 95% CI, 1.8 to 12.4), the presence of additional chest radiographic abnormalities (OR, 3.0; 95% CI, 1.1 to 8.5), and the presence of one or more symptoms suggesting metastasis (OR, 2.6; 95% CI, 1.1 to 6.2). More timely care was not associated with better survival time (adjusted hazard ratio, 1.6; 95% CI, 1.3 to 1.9). However, in patients with SPNs, there was a trend toward better survival time when the time to treatment was < 84 days.

Conclusions: The time to treatment for patients with NSCLC was often longer than recommended. Patients with larger tumors, symptoms, and other chest radiographic abnormalities receive more timely care. In patients with malignant SPNs, survival may be better when treatment is initiated promptly.

Methods: We took a detailed history of smoking habits before AEP onset in 33 patients with AEP, and performed a cigarette smoke provocation test.

Results: Of our AEP patients, all but one (97%) were current smokers. Interestingly, 21 of these were new-onset smokers, and 2 had restarted smoking after a 1- to 2-year cessation of smoking. The duration between starting smoking and AEP onset was within 1 month (0.67 ± 0.53 months). Additionally, six of the remaining smokers had increased the quantity of cigarettes smoked daily, fourfold to fivefold, mostly within the month before AEP onset (0.81 ± 0.58 months). Only three smokers had not changed their smoking habits before AEP onset. Cigarette smoke provocation tests revealed positive results in all nine patients tested.

Conclusion: These data suggest that recent alterations in smoking habits, not only beginning to smoke, but also restarting to smoke and increasing daily smoking doses, are associated with the development of AEP.

Methods: Airway epithelium from non-ADPKD patients was immunostained to localize polycystin-1 expression, and lung tissue from ADPKD patients was examined for pathologic changes. CT scans from ADPKD patients (n = 95) and a control group of non-ADPKD chronic kidney disease patients (n = 95) were retrospectively reviewed for the presence of bronchiectasis using defined criteria.

Results: Immunostaining revealed polycystin-1 expression in the motile cilia of non-ADPKD airway epithelial cells. Lung tissue from one of five available ADPKD patient autopsies revealed histologic changes of bronchiectasis. Review of CT scans revealed a threefold-increased prevalence of bronchiectasis in the ADPKD group compared to the control group (37% vs 13%, p = 0.002).

Conclusions: ADPKD patients demonstrate an increased prevalence of radiographic bronchiectasis, a previously unrecognized manifestation of the disease. This association suggests that patients with primary cilia-associated diseases may be at risk for airway disease.

Methods: This was a double-blind, randomized, placebo-controlled, crossover trial of d-MPH. Patients were seen weekly and completed Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Fatigue Assessment Score (FAS) instruments. After a 1-week wash-in period, patients received either d-MPH or placebo. After 8 weeks, the medications were stopped. Following a 2-week wash-out period, patients were crossed over to 8 weeks of the other treatment. FVC and 6-min walk distance (6MWD) were determined initially and after each treatment arm.

Results: Ten patients with sarcoidosis were enrolled: 8 women and 5 African Americans. All were receiving systemic sarcoidosis therapy. Significant improvement in fatigue was reported by patients when receiving d-MPH (FACIT-F, p < 0.001; FAS, p < 0.02). FVC was higher at the end of 8 weeks of d-MPH compared to the baseline values (baseline median, 2.38 L; range, 1.17 to 4.53 L; placebo median, 2.41 L; range, 1.50 to 4.65 L; d-MPH median, 2.56 L; range, 1.50 to 4.96 L; p < 0.01). There was no significant difference in the 6MWD (baseline median, 330 m; range, 60 to 460 m; placebo median, 350 m; range, 180 to 460 m; d-MPH median, 390 m; range, 200 to 460 m). d-MPH was well tolerated.

Conclusions: Treatment with d-MPH was associated with a significant improvement in sarcoidosis-associated fatigue.

Trial registration: Clinicaltrials.gov Identifier: NCT00361387.

Methods: The subjects were 30 elderly patients with active TB and 100 younger patients with active TB. The QFT-2G test results were analyzed in relation to combined and separate responses to early secretory antigenic target 6-kD (ESAT-6) protein and culture filtrate protein 10 (CFP-10) antigens.

Results: Of the 30 elderly patients with active TB, 27% had a positive tuberculin skin test (TST) result and 77% had a positive QFT-2G test result. Of the 100 younger patients with active TB, 70% had a positive TST result and 87% had a positive QFT-2G test result. Although there was no significant difference between the two patient groups in the positive rate for the QFT-2G test results (p = 0.185), there was a significant difference in the rates of positive TST results between the elderly and younger patients (p = 0.012). The positive test result rate for both ESAT-6 and CFP-10 antigens in the elderly patients (17%) was significantly lower than that in younger patients (37%; p = 0.038). There was an indeterminate result for the QFT-2G test in five elderly patients, and this might have been related to the presence of lymphocytopenia due to underlying disease. A negative result on the QFT-2G test was detected in two elderly patients, and this might have been related to the severity of the active TB.

Conclusion: We confirmed that the QFT-2G test might be a more useful method of diagnosing TB infection than the TST for elderly patients if peripheral lymphocyte counts have been preserved.

Methods: We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis.

Results: One hundred ninety patients (73% men; mean age, 69.0 ± 10.1 years [± SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017).

Conclusions: There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.