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BACKGROUND: The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined. METHODS: Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double-blind, crossover study arms (13 subjects in each arm). Each arm compared two dose levels of inhaled ciclesonide that were administered for 3 weeks with a washout period of 3 to 8 weeks, as follows: (1) 40 vs 160 microg daily; and (2) 80 vs 320 microg daily. Baseline and weekly assessments with exercise challenge and sputum analysis were performed. RESULTS: Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated with EIB severity, and predicted the magnitude and temporal response of EIB to high-dose therapy, but not to low-dose therapy (ie, 40 and 80 microg). Low-dose ICS therapy provided a significant reduction in EIB at 1 week, with little additional improvement thereafter, irrespective of baseline sputum eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of < 5%. The difference between the eosinophilic groups in the magnitude of improvement in EIB was evident after the first week of high-dose ICS therapy and increased with time. CONCLUSIONS: These results suggest that eosinophilic airway inflammation may be important in modifying the severity of EIB and the response to ICS therapy. Measurements of sputum eosinophil percentage may, therefore, be useful in predicting the magnitude and temporal response of EIB to different dose levels of ICSs. Trial registration: clinicaltrial.gov; Identifier: NCT00525772.

Background: Although the incidence of COPD is rapidly increasing in women, knowledge is lacking concerning differences in relative mortality and causes of death in women compared with men. We aimed to analyze differences in relative mortality and cause-specific mortality between men and women on long-term oxygen therapy (LTOT) for COPD.

Methods: Patients starting LTOT for COPD in Sweden between January 1, 1987, and December 31, 2004, were prospectively followed until termination of LTOT or through December 31, 2004. Causes of death according to the Swedish National Causes of Death Register were compared between the study group and the general Swedish population matched for age and sex, with the relative mortality expressed as standardized mortality rates (SMRs).

Results: A total of 7,646 patients, 4,033 women and 3,613 men, were followed for a median of 1.7 years (range 0-18.0). No patient was lost to follow-up. A total of 5,448 patients, 2,745 women and 2,703 men, died. Women had a higher SMR than men: overall mortality, SMR 12.0 (95%, 11.6-12.5) vs 7.4 (95% CI, 7.1-7.6); for respiratory disease, SMR 127.9 (95% CI, 122.4-133.6) vs 66.0 (95% CI, 63.1-69.0); cancer, SMR 3.5 (95% CI, 3.0-3.9) vs 2.2 (95% CI, 1.9-2.5); and cardiovascular disease, SMR 3.7 (95% CI, 3.3-4.1) vs 2.5 (95% CI, 2.3-2.7), respectively.

Conclusions: In severe COPD treated with long-term oxygen, women have higher relative mortality than men both overall and for respiratory disease, as well as for cardiovascular disease and cancer.

This article reviews the research on the relation between indoor air pollution exposure and acute respiratory infection (ARI) in children in developing countries. ARI is a cause of death globally, causing approximately 19% of all deaths before the age of 5 years, according to a World Health Organization estimate. Indoor air pollution from biomass fuels, which is strongly poverty related, has long been regarded as an important risk factor for ARI morbidity and mortality. The empirical base for this view is comparatively narrow, with few empirical studies in relation to the magnitude of the global public health importance of the problem. Most existing reports consistently indicate that indoor air pollution is indeed a risk factor for ARI, but studies are generally small and use indirect indicators of pollution, such as use of biomass fuel or type of stove. Exposure assessment for indoor air pollution in developing countries is recognized as a major obstacle because of high cost and infrastructural limitations to chemical pollution sampling. Use of proxy indicators without measurement support may increase the risk of both misclassification of exposure and of confounding by other poverty-related factors. The issue of sufficient sample size further underlines the need for decisions to invest in this research field. Areas where further research is needed also include exploring qualitatively options for interventions that are culturally and economically acceptable to local communities.

BACKGROUND Passive smoking, or environmental tobacco smoke (ETS), is a risk factor for lung cancer, cardiovascular disease and childhood asthma, but a relationship with COPD has not been fully established.

AIM To study ETS as a risk factor for COPD in never-smokers.

METHODS Data from three cross-sectional studies within the Obstructive Lung Disesease in Northern Sweden (OLIN) database were pooled. Of the 2182 lifelong never-smokers 2118 completed structured interviews and spirometry of acceptable quality. COPD was defined according to the GOLD criteria using post-bronchodilator spirometry. The association of COPD with ETS in single and multiple settings was calculated by multivariate logistic regression adjusting for known risk factors for COPD.

RESULTS COPD prevalence was associated with increased ETS exposure: 4.2% (no ETS), 8.0% (ETS ever at home), 8.3% (ETS at previous work) and 14.7% (ETS ever at home and at both previous and current work), test for trend p=0.003. Exclusion of subjects aged ≥65 years and subjects reporting asthma yielded similar results. ETS in multiple settings, such as ever at home and at both previous and current work was strongly associated to COPD, OR 3.80 (95% CI 1.29-11.2).

CONCLUSIONS In this population-based sample of never-smokers, ETS was independently associated with COPD. The association was stronger for ETS in multiple settings. ETS in multiple settings was, after age, the strongest risk factor for COPD and comparable to personal smoking of up to 14 cigarettes/day in comparable materials. The findings strongly advocate measures against smoking in public places.

STUDY OBJECTIVES: In 1996, researchers in Sweden initiated a collaborative randomized study comparing lung volume reduction surgery (LVRS) and physical training with physical training alone. The primary end point was health status; secondary end points included survival and physiologic measurements.

DESIGN: After an initial 6-week physical training program, researchers' patients were randomized to either LVRS (surgical group [SG]) with continued training for 3 months, or to continued training alone (training group [TG]) for 1 year.

SETTING: All seven thoracic surgery centers in Sweden.

PATIENTS: All patients in Sweden with severe emphysema fulfilling inclusion criteria for LVRS.

INTERVENTIONS: Patients randomized to surgery underwent a median sternotomy, except for a few patients in whom thoracotomy or video-assisted thoracoscopy were performed. In the TG, supervised physical training continued for 1 year; in the SG, supervised physical training continued for 3 months postoperatively.

MEASUREMENTS AND RESULTS: Fifty-three patients were included in each group. Six in-hospital deaths occurred after surgery (12%), and one more death occurred during follow-up. Two deaths occurred in the TG. The difference in death rates between the groups was not statistically significant. Health status, as measured by St. George Respiratory Questionnaire (SGRQ) [total scale score mean difference at 1 year, 14.7; 95% confidence interval (CI), 9.8 to 19.7] as well as by the Medical Outcomes Study Short-Form General Health Survey (physical function scale score mean difference at 1 year, 19.7; 95% CI, 12.1 to 27.3) was improved from baseline in the SG compared with the TG. FEV(1), residual volume, and shuttle walking test values also improved in the SG but not in the TG after 6 months and 12 months.

CONCLUSIONS: In severe emphysema, LVRS can improve health status in survivors but is associated with mortality risk. The effects are stable for at least 1 year. Physical training alone failed to achieve a similar improvement.

BACKGROUND: The study aimed to evaluate the effect of upper extremity resistance training for patients with COPD on dyspnea during activity of daily living (ADL), arm function, arm exercise capacity, muscle strength and health related quality of life (HRQL)

METHODS: Patients were randomly assigned to an intervention or control group. The intervention group underwent arm resistance training. The control group performed a sham. Both groups exercised 3 times a week for 6 weeks. Dyspnea during ADL and HRQL were measured using the chronic respiratory disease questionnaire (CRDQ). Arm function and exercise capacity were measured using the 6-minute pegboard and ring test (6PBRT) and the unsupported upper limb exercise test (UULEX), respectively. Muscle strength for the biceps, triceps, anterior and middle deltoids was obtained using an isometric dynamometer.

RESULTS: Thirty-six patients with COPD (66 +/- 9 yrs) participated in the study. Compared with the control group, the magnitude of change in the intervention group was greater for the 6PBRT (p = 0.03), UULEX (p = 0.01) and elbow flexion force (p = 0.01); elbow extension force (p = 0.02), shoulder flexion force (p = 0.029) and shoulder abduction force (p = 0.01). There was no between-group difference in dyspnea during ADL, HRQL or symptoms during the 6PBRT or UULEX (all p values greater than 0.08).

CONCLUSIONS: Resistance based arm training improved arm function, arm exercise capacity and muscle strength in patients with COPD. No improvement in dyspnea during ADL, HRQL or symptoms was demonstrated.

Background: Patients who have had tuberculosis are at risk for respiratory failure with hypercapnea from chest wall deformity and hypoxia from pulmonary sequelae. The combination of hypercapnea and hypoxia justifies both mechanical ventilation and oxygen therapy as treatment options. We aimed to study which treatment mode is associated with the best survival in patients with the combination of respiratory failure and chest wall deformity from tuberculosis.

Methods: Swedish patients starting oxygen therapy or mechanical ventilation between 1996 and 2004 due to the combination of respiratory failure and chest wall deformity from tuberculosis were eligible for conclusion. They were followed up prospectively until October 2006, with death as the primary outcome. Results: A cohort of 188 patients was included. Eighty-five patients received mechanical ventilation, and 103 received oxygen therapy alone. No patients were excluded, and no patients were unavailable for follow-up. Mechanical ventilation was associated with a significantly better survival than oxygen therapy alone, even after adjustments for age, gender, concomitant respiratory disease, blood gas tensions, and vital capacity, with an adjusted hazard risk of death of 0.35 (95% confidence interval, 0.17 to 0.70).

Conclusion: Patients with the combination of respiratory failure and chest wall deformity from tuberculosis had a significantly better survival when treated with home mechanical ventilation than with long-term oxygen therapy alone. We recommend home mechanical ventilation with or without supplementary oxygen as the first choice of treatment for these patients.

AIM: To estimate the cumulative incidence of COPD and risk factors related to the development of COPD, including evaluation of the relationship between Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 (ie, respiratory symptoms and normal lung function) and the development of COPD, in an age-stratified general population sample of middle-aged and elderly individuals. METHOD: The third survey of the Obstructive Lung Disease in Northern Sweden studies cohort I (three age strata born in 1919 to 1920, 1934 to 1935, and 1949 to 1950) was performed in 1996, and 5,189 subjects (88%) responded to the postal questionnaire. Of the responders, a random sample (1,500 subjects) was invited to an examination in 1996 and in 2003. A total of 963 subjects performed spirometry on both occasions. COPD was defined according to the spirometric criteria of the GOLD. Two levels of disease severity, grade I and higher (GOLD criteria, FEV(1)/FVC ratio of < 0.70) and also grade II and higher (GOLD II criteria, FEV(1)/FVC ratio of < 0.70 and FEV(1) <80% predicted). RESULTS: The 7-year cumulative incidence of COPD was 11.0% and 4.9%, respectively, according to GOLD and GOLD II, and was significantly related to smoking (smokers, 18.8% and 10.6%, respectively; ex-smokers, 10.5% and 5.2%, respectively; non-smokers, 7.6% and 1.6%, respectively). Incident COPD according to GOLD, but not according to GOLD II, was significantly associated with increasing age. Most respiratory symptoms at study entry were markers of increased risk for incident COPD when analyzed in a multivariate model adjusting for confounders. CONCLUSION: The GOLD criteria yielded a higher cumulative incidence (11.0%) compared to the GOLD II (4.9%). Smoking, but not gender, was associated with incident COPD. Most respiratory symptoms at the beginning of the observation period marked an increased risk for developing COPD, thus the classification GOLD stage 0 seems relevant among middle-aged and elderly persons.

STUDY OBJECTIVES: To determine the 10-year cumulative incidence of COPD in a cohort of subjects with respiratory symptoms (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 0) using the British Thoracic Society (BTS) and GOLD spirometric criteria. Furthermore, we sought to evaluate risk and gender factors for incident COPD. DESIGN AND SETTING: A postal questionnaire was administered in 1986 to all 6,610 subjects in eight areas of northern Sweden who had been born in 1919 to 1920 (group 1), 1934 to 1935 (group 2), and 1949 to 1950 (group 3). The response rate was 86%. All of the subjects reporting respiratory symptoms were invited to participate in a structured interview and pulmonary function test (PFT), and 1,506 (91%) participated. In 1996, 90% could be traced for follow-up, of whom 1,165 (86%) of the invited subjects participated and 1,109 subjects (534 women) were able to perform technically adequate PFTs in both 1986 and 1996. RESULTS: The 10-year cumulative incidence of COPD was estimated at 8.2% (using BTS criteria) and 13.5% (using GOLD criteria). Significant risk factors for incident COPD (using BTS and GOLD criteria) in a multivariate analysis were higher age (group 1 odds ratio [OR]: BTS criteria, 3.49; GOLD criteria, 3.37; group 2 OR: BTS criteria, 4.50; GOLD criteria, 5.70) and smoking (OR: BTS criteria, 5.37; GOLD criteria, 4.56), but not gender or heredity. Respiratory symptoms were significantly associated with incident COPD when added to the same model. In analogous analyses that were conducted separately for men and women, smoking yielded an OR of 8.52 among women (95% confidence interval [CI], 3.43 to 21.2) compared with 3.14 among men (95% CI, 1.26 to 7.84). The symptoms cough, sputum production, and chronic productive cough reached statistical significance in women, while dyspnea and wheeze did so in men. CONCLUSION: In this cohort, the 10-year cumulative incidence of COPD was 8.2% (using BTS criteria) and 13.5% (using GOLD criteria). Increasing age, smoking, and bronchitic symptoms, but not gender, were risk factors for incident COPD. GOLD stage 0 therefore appears to identify subjects who are at risk of COPD, but men and women presented different risk profiles.

Background: Cardiopulmonary involvement in patients with systemic sclerosis (SSc) carries a poor prognosis, mainly due to pulmonary hypertension and tight-heart failure. To date, light ventricular (RV) involvement has not been studied in detail. We therefore assessed RV function in patients with SSc and related the findings to the clinical features of the disease. Method: Twenty-six consecutive patients (21 women) with SSc (mean age, 56 15 years [+/- SD]) and 25 healthy, age-matched control subjects (21 women) were studied. Doppler echocardiography including Doppler tissue imaging was used to evaluate cardiac function. Pulmonary function was also studied. Results: Compared with control subjects, RV free wall thickness (5.8 +/- 1.7 mm vs 3.7 +/- 1.1 mm, p < 0.001) and right atrial (RA) systolic area (15.9 +/- 3.7 cm(2) vs 13.0 +/- 2.3 cm(2), P < 0.01) were increased in patients with SSc, while the global early diastolic/atrial component velocity ratio was reduced (1.2 +/- 0.4 vs 1.7 +/- 0.6, p < 0.01). The global isovolumic relaxation time (IVRT) [64 23 ms vs 39 +/- 13 ms, p < 0.001] and regional IVRT (83 +/- 40 ins vs 46 +/- 24 ms, p < 0.001) were prolonged in patients vs control subjects, whereas the RV global filling time was reduced (454 +/- 122 ins vs 548 104 ins, p < 0.01). RV systolic function and pulmonary pressures at rest were similar in the two groups, but the pulmonary artery acceleration time was reduced (119 +/- 34 ins vs 141 +/- 29 ins, p < 0.05) in patients compared to control subjects. Left ventricular function did not differ between the two groups. Conclusion: Patients with SSc exhibit altered RV diastolic function together with an increase in RV wall thickness and RA area. These findings appear to be early markers of RV disturbance, probably in response to intermittent pulmonary arterial hypertension.

BACKGROUND: Cardiopulmonary involvement in patients with systemic sclerosis (SSc) carries a poor prognosis, mainly due to pulmonary hypertension and right-heart failure. To date, right ventricular (RV) involvement has not been studied in detail. We therefore assessed RV function in patients with SSc and related the findings to the clinical features of the disease. METHOD: Twenty-six consecutive patients (21 women) with SSc (mean age, 56 +/- 15 years [+/- SD]) and 25 healthy, age-matched control subjects (21 women) were studied. Doppler echocardiography including Doppler tissue imaging was used to evaluate cardiac function. Pulmonary function was also studied. RESULTS: Compared with control subjects, RV free wall thickness (5.8 +/- 1.7 mm vs 3.7 +/- 1.1 mm, p < 0.001) and right atrial (RA) systolic area (15.9 +/- 3.7 cm2 vs 13.0 +/- 2.3 cm2, p < 0.01) were increased in patients with SSc, while the global early diastolic/atrial component velocity ratio was reduced (1.2 +/- 0.4 vs 1.7 +/- 0.6, p < 0.01). The global isovolumic relaxation time (IVRT) [64 +/- 23 ms vs 39 +/- 13 ms, p < 0.001] and regional IVRT (83 +/- 40 ms vs 46 +/- 24 ms, p < 0.001) were prolonged in patients vs control subjects, whereas the RV global filling time was reduced (454 +/- 122 ms vs 548 +/- 104 ms, p < 0.01). RV systolic function and pulmonary pressures at rest were similar in the two groups, but the pulmonary artery acceleration time was reduced (119 +/- 34 ms vs 141 +/- 29 ms, p < 0.05) in patients compared to control subjects. Left ventricular function did not differ between the two groups. CONCLUSION: Patients with SSc exhibit altered RV diastolic function together with an increase in RV wall thickness and RA area. These findings appear to be early markers of RV disturbance, probably in response to intermittent pulmonary arterial hypertension.

Objective: To evaluate the effects of a mandibular advancement device on apneas and sleep in, mild, moderate and severe obstructive sleep apnea.

Design: Prospective study.

Subjects: Forty-four of 47 patients included.

Intervention: Individually adjusted mandibular advancement devices.

Measurements: Polysomnographic sleep recordings for 1 night without the device and 1 night with it, with a median of 1 day and no changes in weight, medication, or sleep position between the recordings.

Results: The device reduced the median apnea-hypopnea index from 11 (range, 7 to 19) to 5 (range, 0 to 17) (p<0.001) in 21 patients with mild sleep apnea, from 27 (range, 20 to 38) to 7 (range 1 to 19) (p<0.001) in 15 patients with moderate sleep apnea, and from 53 (range 44 to 66) to 14 (range, 2 to 32) (p=<0.05) in 8 patients with severe sleep apnea. The arousal index decreased and the sleep stage patterns improved in all severity groups. Twenty-eight of 44 patients were successfully treated with an obstructive apnea-hypopnea index of below 10 and a subjective reduction in snoring. Nine of 16 patients with treatment failure still reported a reduction in snoring. The success rate correlated inversely to the disease severity (r=-0.41; p<0.01).

Conclusions: A mandibular advancement device reduces apnea and improves sleep quality in patients with obstructive sleep apnea, especially in those with mild and moderate disease. A follow-up sleep recording during treatment is necessary because of the risk of silent obstructive apneas without subjective snoring with the device.

Background: Training volume is paramount in the magnitude of physiological adaptations following resistance training. However, patients with severe COPD are limited by dyspnea during traditional two-limb low-load/high-repetition resistance training (LLHR-RT), resulting in suboptimal training volumes. During a single exercise session, single-limb LLHR-RT decreases the ventilatory load and enables higher localized training volumes compared with two-limb LLHR-RT.

Research Question: Does single-limb LLHR-RT lead to more profound effects compared with two-limb LLHR-RT on exercise capacity (6-min walk distance [6MWD]), health status, muscle function, and limb adaptations in patients with severe COPD?

Study Design and Methods: Thirty-three patients (mean age 66 ± 7 years; FEV1 39 ± 10% predicted) were randomized to 8 weeks of single- or two-limb LLHR-RT. Exercise capacity (6MWD), health status, and muscle function were compared between groups. Quadriceps muscle biopsy specimens were collected to examine physiological responses.

Results: Single-limb LLHR-RT did not further enhance 6MWD compared with two-limb LLHR-RT (difference, 14 [–12 to 39 m]. However, 73% in the single-limb group exceeded the known minimal clinically important difference of 30 m compared with 25% in the two-limb group (P = .02). Health status and muscle function improved to a similar extent in both groups. During training, single-limb LLHR-RT resulted in a clinically relevant reduction in dyspnea during training compared with two-limb LLHR-RT (–1.75; P = .01), but training volume was not significantly increased (23%; P = .179). Quadriceps muscle citrate synthase activity (19%; P = .03), hydroxyacyl-coenzyme A dehydrogenase protein levels (32%; P < .01), and capillary-to-fiber ratio (41%; P < .01) were increased compared with baseline after pooling muscle biopsy data from all participants.

Interpretation: Single-limb LLHR-RT did not further increase mean 6MWD compared with two-limb LLHR-RT, but it reduced exertional dyspnea and enabled more people to reach clinically relevant improvements in 6MWD. Independent of execution strategy, LLHR-RT improved exercise capacity, health status, muscle endurance, and enabled several physiological muscle adaptations, reducing the negative consequences of limb muscle dysfunction in COPD.

BACKGROUND: Hantaviruses cause two clinical syndromes; hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The clinical spectrum in HFRS also often involves respiratory symptoms. As information of the pulmonary pathogenesis in HFRS is limited, we aimed to further study the local airway immune response in the lower airways.

METHODS: In 15 hospitalized HFRS patients, bronchoscopy was performed with sampling of endobronchial mucosal biopsies and bronchoalveolar lavage (BAL) fluid. Biopsies were stained for leukocytes, lymphocyte subsets and vascular endothelial adhesion molecules. BAL fluid and blood lymphocyte subsets were determined using flow cytometry. Fourteen healthy volunteers acted as control group.

RESULTS: Compared to controls, endobronchial mucosal biopsies from HFRS patients revealed increased numbers of CD8(+) T cells in both epithelium and submucosa (p≤0.001), along with an increase in submucosal CD4(+) T cells (p=0.001). In contrast, patients' submucosal neutrophil and eosinophil numbers were reduced (p<0.001). The expression of vascular cell adhesion molecule-1 (VCAM-1) was enhanced in HFRS patients (p<0.001). In HFRS patients, analyses of T cell subsets in BAL fluid showed higher proportions of CD3(+) and CD8(+) T cells (p=0.011 and p=0.025), NK cells (p<0.001) together with an increased expression of activation markers HLA-DR and CD25 on T cells (p<0.001 and p<0.001).

CONCLUSIONS: The present findings indicate a local immune response in terms of activated T lymphocytes in the lungs of patients with HFRS. The elevated expression of activation markers and VCAM-1 further implies the importance of cytotoxic lymphocytes in the pathogenesis of pulmonary involvement in HFRS.

Background: No large prospective data, to our knowledge, are available on ventilator-associated pneumonia (VAP) in patients with traumatic brain injury (TBI).

Research Question: To evaluate the incidence, timing, and risk factors of VAP after TBI and its effect on patient outcome.

Study Design and Methods: This analysis is of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury data set, from a large, multicenter, prospective, observational study including patients with TBI admitted to European ICUs, receiving mechanical ventilation for ≥ 48 hours and with an ICU length of stay (LOS) ≥ 72 hours. Characteristics of patients with VAP vs characteristics of patients without VAP were compared, and outcome was assessed at 6 months after injury by using the Glasgow Outcome Scale Extended.

Results: The study included 962 patients: 196 (20.4%) developed a VAP at a median interval of 5 days (interquartile range [IQR], 3-7 days) after intubation. Patients who developed VAP were younger (median age, 39.5 [IQR, 25-55] years vs 51 [IQR, 30-66] years; P < .001), with a higher incidence of alcohol abuse (36.6% vs 27.6%; P = .026) and drug abuse (10.1% vs 4.2%; P = .009), more frequent thoracic trauma (53% vs 43%; P = .014), and more episodes of respiratory failure during ICU stay (69.9% vs 28.1%; P < .001). Age (hazard ratio [HR], 0.99; 95% CI, 0.98-0.99; P = .001), chest trauma (HR, 1.4; 95% CI, 1.03-1.90; P = .033), histamine-receptor antagonist intake (HR, 2.16; 95% CI, 1.37-3.39; P = .001), and antibiotic prophylaxis (HR, 0.69; 95% CI, 0.50-0.96; P = .026) were associated with the risk of VAP. Patients with VAP had a longer duration of mechanical ventilation (median, 15 [IQR, 10-22] days vs 8 [IQR, 5-14] days; P < .001) and ICU LOS (median, 20 [IQR, 14-29] days vs 13 [IQR, 8-21] days; P < .001). However, VAP was not associated with increased mortality or worse neurological outcome. Overall mortality at 6 months was 22%.

Interpretation: VAP occurs less often than previously described in patients after TBI and has a detrimental effect on ICU LOS but not on mortality and neurological outcome.

Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02210221; URL: www.clinicaltrials.gov

BACKGROUND: The pathophysiologic mechanism of nocturnal obstruction and swallowing dysfunction commonly occurring in patients with sleep apnea is unclear. The goal of this study was to investigate whether nerve injuries in the upper airways of snorers and patients with sleep apnea are associated with pharyngeal dysfunction and severity of sleep apnea.

METHODS: Twenty-two patients undergoing palatal surgery due to snoring and sleep apnea were investigated for a swallowing dysfunction by using videoradiography. Twelve healthy nonsnoring subjects were included as control subjects. Tissue samples from the soft palate at the base of the uvula were obtained in all patients and control subjects. Nerves and muscle were analyzed with immunohistochemical and morphologic methods, and the findings were correlated with swallowing function and degree of sleep apnea.

RESULTS: In the soft palate of patients, nerve fascicles exhibited a significantly lower density of axons (5.4 vs 17.9 x 10(-3) axons/mu m(2); P = .02), a smaller percentage area occupied by Schwann cells (17.5% vs 45.2%; P = .001) and a larger number of circular shaped Schwann cells lacking central axons (43.0% vs 12.7%; P < 0.001) compared with control subjects. The low density of axons was significantly related to degree of swallowing dysfunction (r = 0.5; P = .03) and apnea-hypopnea index > 5 (P = .03). Regenerating axons were frequently observed in patients compared with control subjects (11.3 +/- 4.2% vs 4.8 +/- 2.4%; P = .02).

CONCLUSIONS: Axon degeneration in preterminal nerves of the soft palate is associated with pharyngeal dysfunction in snorers and patients with sleep apnea. The most likely cause for the nerve injuries is traumatic snoring vibrations and tissue stretch, leading to swallowing dysfunction and increased risk for upper airway obstruction during sleep.

BACKGROUND: The prevalence of COPD is estimated to 4 to 14%. According to the Global Initiative for Chronic Obstructive Lung Disease guidelines, COPD is divided into four stages. Patients with stage IV disease (very severe) have FEV1 < 30% of predicted values and/or respiratory insufficiency. The few studies that exist have reported a stage IV disease prevalence of 0.1 to 0.2% but provide limited additional patient characteristics. The present study estimated the prevalence of physician-diagnosed stage IV COPD in the city of Ostersund, Sweden, and characterized the patients.

METHODS: Due to the regional integrated care pathway, patients in whom severe COPD is diagnosed are under surveillance by the Respiratory Department at Ostersund Hospital. Among these patients and all others in whom COPD has been diagnosed at Ostersund Hospital from 2000 to 2004, all those with an FEV1 of < 40% predicted were examined.

RESULTS: A total of 76 patients fulfilled the criteria for stage IV COPD. The mean age was 71 years, 59% were women, and 40% were receiving long-term oxygen therapy. Sixty-five percent of the patients lived independently at home, 9% were present smokers, and 75% used inhaled corticosteroids daily. Sixty-seven percent of the patients had received vaccination against influenza the previous year. During 2004, 48% of the patients had at least one COPD-related hospitalization, and 11% had made at least one visit to the hospital for emergency care.

CONCLUSIONS: The present study indicated that 0.13% of the population in Ostersund in 2004 had physician-diagnosed stage IV COPD. This is probably an underestimation of the true prevalence. Patients with stage IV COPD appear to require periods of hospitalization more often than intermittent emergency department visits.

OBJECTIVES: The aim was to investigate the significance of snoring and sleep apnea on daytime symptoms in a population-based sample of women. METHOD: From the general population, 400 women aged 20 to 70 years were randomly selected, with oversampling of habitually snoring women. The women were investigated using 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. RESULTS: Habitual snoring was independently related to excessive daytime sleepiness (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.31 to 3.99), to falling asleep involuntarily during the day (OR, 2.11; 95% CI, 1.06 to 4.21), to waking up unrefreshed (OR, 2.14; 95% CI, 1.30 to 3.52), to daytime fatigue (OR, 2.77; 95% CI, 1.54 to 4.99), and to a dry mouth on awakening (OR, 2.00; 95% CI, 1.22 to 3.27) after adjustment for AHI, age, body mass index (BMI), smoking, total sleep time, percentage of slow-wave sleep, and percentage of rapid eye movement (REM) sleep. An AHI > or = 15/h was only related to a dry mouth on awakening after adjustment for snoring, age, BMI, smoking, total sleep time, percentage of slow-wave sleep, and percentage of REM sleep (OR, 2.24; 95% CI, 1.14 to 4.40). An AHI of 5 to 15/h was not related to any daytime symptom. CONCLUSIONS: 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 AHI. This indicates that snoring is an independent cause of excess daytime sleepiness and not merely a proxy for sleep apnea.

OBJECTIVES: The aim of the present study was to elucidate whether occupational exposure to vapors, gases, dusts and fumes increases the mortality risk for chronic obstructive pulmonary disease (COPD), especially among never-smokers.

METHODS: The study population was a cohort of 354,718 male construction workers; of these 196,329 were exposed to vapors, gases, dusts and fumes and 117,964 were unexposed. Exposure to inorganic dust, wood dust, vapors, fumes and gases, and irritants was based on a job-exposure matrix with a focus on exposure in the mid-1970s. The cohort was followed from 1972 to 2011. Relative risks (RR) were obtained using Poisson regression models adjusting for age, body mass index and smoking habits.

RESULTS: There were 1,085 deaths from COPD among the exposed workers, including 49 never-smokers. Workers with any occupational exposure to vapors, gases, fumes and dust showed an increased mortality due to COPD (RR=1.32, 95% confidence interval (CI) 1.18-1.47). When comparing different exposure groups, there was a significantly increased mortality due to COPD among those exposed to fumes (RR 1.20, 95% CI 1.07-1.36) and inorganic dust (RR 1.19, 95% CI 1.07-1.33) . Among never-smokers, there was high mortality due to COPD among workers with any occupational airborne exposure (RR 2.11, 95% CI 1.17-3.83). The fraction of COPD attributable to occupational exposure was 0.24 among all workers and 0.53 among never-smoking workers.

CONCLUSIONS: Occupational exposure to airborne pollution increases the mortality risk for COPD, especially among never-smokers.