Respiratory Medicine - Articles in Press

Air pollution and children's respiratory symptoms in six cities of Northern China - Corrected Proof

2010-09-01

Summary: OBJECTIVE: The associations between air pollution and children’s respiratory health in the high pollution range have not yet been clearly characterized. We evaluated the effects of outdoor air pollution on respiratory morbidity in children selected from multiple sites in a heavy industrial province of northeastern China.METHODS: The study included 11,860 children aged 3–12 years, selected from 18 districts of 6 cities in Liaoning province, the participation rate is 89.9%. Informed consent and written responses to surveys about children’s historic and current health status, personal and household characteristics, and other information were obtained from parents. A two-stage regression approach was applied in data analyses.RESULTS: There were wide gradients for TSP (188–689 μg/m3), SO2 (14–140 μg/m3 and NO2 (29–94 μg/m3) across the 18 districts of 6 cities. The three air pollutants significantly increased the prevalence of persistent cough (21–28%), persistent phlegm (21–30%) and current asthma (39–56%) for each interquartile range increment (172 μg/m3 for TSP, 69 μg/m3 for SO2, 30 μg/m3 for NO2), showing larger between-city effects than within-city. Rates of respiratory symptoms were significantly higher for children with younger age, atopy, respiratory disease in early age, family history of asthma or chronic bronchitis, and tobacco smoke exposure.CONCLUSION: The high levels of outdoor air pollution in north China are positively associated with children’s respiratory symptoms, the associations with TSP appear to be stronger than SO2 and NO2.

Factors that prognosticate mortality in idiopathic pulmonary arterial hypertension: A systematic review of the literature - Corrected Proof

John Robert Swiston, Sindhu R. Johnson, John T. Granton — 2010-09-01

Summary: Rationale: There is a lack of consensus on factors that predict mortality in idiopathic pulmonary arterial hypertension (IPAH). Tests that can accurately predict prognosis are needed to guide treatment and counsel patients.Methods: We conducted a systematic review to identify factors that prognosticate mortality in IPAH. Study design, cohort size, comparison method, measured value, and statistical significance was extracted for eight pre-selected parameters [pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), mean right atrial pressure (mRAP), cardiac output, right ventricular end diastolic pressure, functional class, 6 min walk distance (6MWD), and diffusing capacity of carbon monoxide].Results: 107 factors have been associated with mortality in IPAH. A reproducible predictive association with mortality was demonstrated for only 10 factors: functional class (14 studies), heart rate (10 studies), 6MWD (8 studies), pericardial effusion (5 studies), mPAP (10 studies), mRAP (17 studies), cardiac index (13 studies), stroke volume index (4 studies), PVR (10 studies), mixed venous PaO2 or saturations (4 studies). Of the 8 factors chosen for detailed evaluation, there were at least half as many studies that evaluated the variable and did not find an association with mortality compared to those that did.Conclusions: There is a large body of literature describing numerous factors that predict mortality in IPAH. Most factors have been assessed in very few studies. There are conflicting reports on the prognostic value of many factors. These discrepancies highlight the need to evaluate the literature in total when considering the utility of variables as prognostic factors in IPAH.

Elevated HDL cholesterol levels are associated with osteoporosis in lung transplant candidates with chronic obstructive pulmonary disease - Corrected Proof

Robert M. Reed, Robert A. Wise, Adrian S. Dobs, Noah Lechtzin, Reda E. Girgis — 2010-09-01

Summary: Background: Osteoporosis is common in advanced COPD and worsens rapidly after transplantation, potentially impairing quality of life. Increased high density lipoprotein cholesterol (HDLc) has been observed in COPD and linked with osteoporosis in the general population. This association has not been previously examined in COPD.Methods: We reviewed the records of 245 COPD patients referred for lung transplant evaluation. Osteoporosis was defined by either dual energy X-ray absorptiometry scan or use of osteoporosis medications. The presence or absence of osteoporosis could be ascertained in 152 subjects. Cholesterol values and other clinical variables were assessed for their association with osteoporosis.Results: Clinical factors associated with osteoporosis included lower BMI [OR 0.81, 95% CI 0.73–0.90], higher HDLc [OR 1.04, 95% CI 1.02 to 1.07], and worse lung function. HDLc was an independent predictor of OP and demonstrated an inverse linear correlation with T-scores (r = −0.21, p = 0.05), which was stronger amongst males (r = −0.45, p = 0.004).Conclusion: In COPD patients referred for lung transplantation, osteoporosis is highly prevalent. Raised HDLc levels are common in this group and are independently associated with OP.

Behaviour and survival of high-grade neuroendocrine carcinomas of the lung - Corrected Proof

J.M. Naranjo Gómez, J.J. Gómez Román — 2010-09-01

Summary: Introduction: Large-cell neuroendocrine carcinoma is an aggressive variant of large-cell carcinoma of the lung, which has poor survival in most series, resembling that of small-cell lung carcinoma. We report our retrospective assessment of surgically-resected cases of both tumours.Methods: 33 large-cell neuroendocrine carcinomas and 16 peripheral small-cell lung carcinomas were reassessed retrospectively. Survival rates of both tumours in surgically-resected cases were calculated and compared using Kaplan–Meier survival curves and Log Rank test, respectively.Results: In large-cell neuroendocrine carcinomas, there were 25 patients with pathologic stage I, 4 with pathologic stage II and 4 with pathologic stage III. In small-cell lung carcinomas, there were 6 patients with pathologic stage I, 3 with pathologic stage II and 7 with pathologic stage III. 12% of large-cell neuroendocrine carcinomas and 62.5% of small-cell lung carcinomas were of advanced disease. The mean follow-up was 89 months. The actuarial survival for the 2 groups was not significantly different.Conclusion: Large-cell neuroendocrine carcinomas of the lung have poor prognosis even in early stages, with survival rates similar to that of small-cell lung carcinomas.

Omalizumab-induced decrease of FcɛRI expression in patients with severe allergic asthma - Corrected Proof

2010-08-30

Summary: Background: It is documented that omalizumab treatment reduces the cell surface expression of immunoglobulin E high-affinity receptor (FcɛRI) on several cell types. This has not been investigated in patients with uncontrolled severe persistent allergic asthma.Methods: In a double-blind, randomized, placebo-controlled study, patients with severe allergic asthma uncontrolled by high dose inhaled corticosteroids and long-acting β2-agonist received either omalizumab (n = 20) or placebo (n = 11) over 16 weeks at appropriate doses and frequencies. Baseline and end of study (week 16) FcɛRI expression on basophils and plasmacytoid dendritic cells was determined by flow cytometry for the primary endpoint. Secondary efficacy endpoints included asthma control and lung function as part of an initial investigation into the use of FcɛRI expression as a marker of response.Results: In the omalizumab group, and with respect to placebo, FcɛRI expression was significantly reduced at end of study on basophils (−82.6%, p < 0.01) and plasmacytoid dendritic cells (−44.2%, p = 0.029). FcɛRI expression reduction was not found to be correlated with clinical response.Conclusions: Long-term omalizumab treatment induced reduction of FcɛRI expression on circulating basophils and plasmacytoid dendritic cells. These changes were not associated with those of clinical features related to severe asthma, which does not support further investigation into its use as a predictive marker of response.Trial registration: The study was registered with ClinicalTrials.gov (identifier: NCT00454051) and the European Clinical Trials Database, EudraCT (identifier: 2006-003591-35)

The Physicians’ Practice Assessment Questionnaire on asthma and COPD - Corrected Proof

Louis-Philippe Boulet, Hollie Devlin, Denis E. O’Donnell — 2010-08-27

Summary: We describe a new tool, the Physicians’ Practice Assessment Questionnaire (PPAQ), designed for the global self-assessment of implementation of asthma and COPD guidelines, as determined by the percentage of patients in whom physicians estimate that they implement guidelines key recommendations. Some of its properties were assessed by a group of 47 general practitioners (GPs), and test–retest data were obtained in repeating the questionnaire at a 5-week interval without intervention in a sub-group of 28 practitioners. Answers to the various questions were globally reproducible. The lowest scores (recommendations implemented in less than 50% of their patients) were: 1) for both asthma and COPD: referral for patient education, provision of a written action plan and regular assessment of inhaler technique, 2) for asthma: referral to a specialist for difficult to control asthma or uncertain diagnosis, and 3) for COPD: assessment of lung function and disability according to specific criteria and referral to a rehabilitation program. The analysis showed sufficient internal consistency for both questionnaires (Cronbach alphas 0.7617 for asthma and 0.8317 for COPD). Pearson’s correlations indicated good test–retest (r = 0.6421, p = 0.0002 for asthma; r = 0.6801, p < 0.0001 for COPD). In conclusion, the PPAQ is a new tool to assess implementation of asthma and COPD guidelines; it has the potential to identify care gaps that can be specifically targeted for intervention.

Omalizumab treatment and exercise capacity in severe asthmatics – Results from a pilot study - Corrected Proof

2010-08-27

Summary: Background: In patients with moderate to severe allergic asthma, clinical effectiveness of omalizumab, an approved anti-IgE-reacting substance, is usually assessed by pulmonary function testing (PFT), symptom scores and physicians judgement.Aims: We postulate that cardiopulmonary exercise testing (CPET) may provide an additional option to verify symptomatic changes in patients with allergic asthma.Methods: Ten consecutive patients with allergic asthma were treated with omalizumab. Prior to and after 16 weeks of treatment all patients underwent PFT and symptom-limited CPET. Results were compared to 10 asthmatic controls without omalizumab medication. Symptoms were assessed according to investigators judgement (IGETE).Results: All 20 patients showed a significantly impaired exercise capacity at baseline [peak oxygen uptake (VO2) 71 ± 16% predicted]. In patients with omalizumab, peakVO2 increased from 13.8 (8.4–21.4) to 16.8 (11.2–23.9) ml/kg/min (p < 0.05), VO2 at anaerobic threshold increased by 22% [9.8 (3.3–15.2) to 12.3 (6.7–14.4) ml/kg/min (p < 0.05)]. There was no improvement in the controls. The increase in VO2 was significantly correlated to the improvement in symptoms. All patients revealed dynamic hyperinflation under exercise with a decreasing extent with omalizumab treatment.Conclusion: This study suggests that CPET may provide additional and useful tools to assess and verify the individual clinical response to omalizumab treatment. An improvement in exercise capacity can reliably mirror changes in quality of life and IGETE. Patients with omalizumab experience significant improvements in their initially impaired exercise capacity. CPET can be safely accomplished in patients with severe asthma.

Exercise decreases plasma antioxidant capacity and increases urinary isoprostanes of IPF patients - Corrected Proof

R. Jackson, C. Ramos, C. Gupta, O. Gomez-Marin — 2010-08-26

Summary: We tested whether markers of systemic oxidant stress were detectable in 29 typical IPF patients, and whether these increased after low level exercise. We obtained resting plasma for measurement of amino terminal pro brain natriuretic peptide (NT-proBNP), and plasma and urine samples for isoprostanes and total nitrite. Total antioxidant capacity (TAC) was measured in plasma, and H2O2 was measured in urine. Subjects exercised at ˜50 W on a semi recumbent bicycle until limited by dyspnea. Samples were obtained immediately after exercise for measurement of the same variables.Plasma and urine samples were also obtained at rest from 6 normal individuals over 40 years of age solely to establish comparison values for NT-proBNP, nitrite, H2O2 and TAC assays.Plasma NT-proBNP was high at rest and after exercise, suggesting pulmonary arterial hypertension. IPF patients’ resting NT-proBNP concentrations apparently exceeded those of normal controls. IPF plasma isoprostanes at rest exceeded the normals. IPF urine isoprostanes increased significantly after exercise (P = 0.047 by signed rank test); and, plasma TAC decreased significantly after exercise (P < 0.001 by signed rank test). Neither plasma nor urine nitrite changed significantly after exercise. H2O2 concentration was quite high after exercise in some IPF subjects’ urine.IPF patients demonstrate systemic oxidant stress at rest detectable as increased isoprostanes in the circulation. An increase in urine isoprostanes and a decrease in plasma TAC after exercise suggest that reactive oxygen species (ROS) are produced during low level exercise done by IPF patients.

Effect of tonsillectomy on the level of exhaled nitric oxide (NO) in patients with recurrent tonsillitis - Corrected Proof

A. Kasperska-Zajac, E. Czecior, G. Namyslowski — 2010-08-23

Summary: Background: Increased expression of inducible nitric oxide synthase in inflamed tonsils has been reported. Our preliminary observation was the first to demonstrate that increased exhaled NO level may occur in patients with tonsillitis.Objective: To extend the observation scope, the same group of patients was examined for NO exhaled after tonsillectomy.Materials and Methods: Exhaled oral NO level was measured with Niox Mino® analyzer, six-seven months after tonsillectomy in 27 non-atopic patients who suffered from recurrent tonsillitis and in 35 healthy non-atopic subjects.Results: After tonsillectomy, exhaled NO levels were significantly reduced as compared to the preoperative period values and did not differ significantly from those of the healthy subjects.Conclusions: The results support a finding of the elevated exhaled NO consequent to NO production in chronically inflamed tonsils, but whether NO plays any role in the pathogenesis of tonsillitis or is merely a by-product of another process, needs to be determined.

COPD in young patients: A pre-specified analysis of the four-year trial of tiotropium (UPLIFT) - Corrected Proof

A.H. Morice, B. Celli, S. Kesten, T. Lystig, D. Tashkin, M. Decramer — 2010-08-19

Summary: Whilst recent large-scale studies have provided much evidence on the natural history and therapeutic response in patients with chronic obstructive pulmonary disease (COPD), relatively little is known about the effect in younger patients.We report a pre-specified post-hoc analysis of 356 patients with COPD ≤ 50 years old from the four year randomised, double blind placebo controlled Understanding Potential Long Term Impact on Function with Tiotropium (UPLIFT) trial. Inclusion criteria included a post-bronchodilator forced expiratory volume in 1 s (FEV1) of ≤70%, FEV1/FVC < 0.70, age ≥40 years, and smoking history of ≥10 pack years.Younger patients had a mean FEV1 of 1.24 L (39% predicted) and an impaired health-related quality of life (St. George’s Respiratory Questionnaire (SGRQ)) compared to the entire UPLIFT population. There were 40.2% women and 51.1% current smokers in the younger age group. Tiotropium was associated with a sustained improvement in spirometry and SGRQ. Mean decline in post-bronchodilator FEV1 was 58 ml/year (placebo) vs. 38 ml/year (tiotropium) (p = 0.01). Corresponding values for pre-bronchodilator FEV1 were 41 ml/year (placebo) compared with 34 ml/year (tiotropium) (p = 0.34). The hazard ratio (95%CI) for an exacerbation in the younger age group was 0.87(0.68, 1.13)). The rate of exacerbations was reduced by tiotropium (rate ratio (95%CI) = 0.73(0.56, 0.95)).Tiotropium resulted in sustained bronchodilation, improved quality of life, and a decreased exacerbation rate in younger patients. Tiotropium also resulted in a significant reduction in the decline in post-bronchodilator FEV1, suggesting possible disease modification by tiotropium in younger patients with COPD.

The cyclooxygenase-2-765C promoter polymorphism protects against the development of chronic obstructive pulmonary disease - Corrected Proof

Lian Wu, Mervyn Merrilees, Robert P. Young, Peter N. Black — 2010-08-19

Summary: Background: Susceptibility to Chronic Obstructive Pulmonary Disease (COPD) has a genetic component. We undertook a study to determine if a genetic variant of the gene encoding the cyclooxygenase-2 gene influences the likelihood of developing COPD.Methods: In a case control study the frequency of a single nucleotide polymorphism in the promoter region of the cyclooxygenase-2 gene (-765 G → C) was determined in 205 subjects with COPD, 171 chronic smokers with normal lung function (resistant smokers) and 95 healthy blood donors using the polymerase chain reaction and restriction enzyme fragment length polymorphism.Results: The frequency of the C allele of the -765 cyclooxygenase-2 polymorphism was higher in resistant smokers (24.6%) compared with subjects with COPD (14.4%, OR = 1.98, 95% CI = 1.28–3.06, p = 0.003) and blood donors (14.7%, OR = 1.97, 95% CI = 1.14–3.41, p = 0.03).Conclusions: The -765C allele, which has been shown to be associated with decreased promoter activity of the cyclooxygenase-2 gene, is more common in resistant smokers. This raises the possibility that decreased activity of cyclooxygenase-2 may protect smokers against the development of COPD.

Lactate dehydrogenase as prognostic factor in limited and extensive disease stage small cell lung cancer – A retrospective single institution analysis - Corrected Proof

Andreas Hermes, Ulrich Gatzemeier, Benjamin Waschki, Martin Reck — 2010-08-18

Summary: Purpose: The aim of this retrospective study is to present data on clinical significance of lactate dehydrogenase (LDH) serum levels in an unselected contemporary patient population with small cell lung cancer (SCLC) in limited disease (LD) and extensive disease stage (ED).Patients and methods: From June 2004 to June 2008, our electronic database including all in-patient and out-patient contacts was searched for patients with newly diagnosed LD and ED SCLC. 397 cases were identified. We collected data on patient characteristics including clinical performance status and LDH serum levels, metastatic sites, efficacy of first line chemotherapy and survival.Results: In both limited and extensive disease SCLC, elevated LDH serum levels resulted in significantly shorter median survival. The effect was most pronounced if levels were 300 U/l or higher. In patients with limited disease and normal LDH levels, median survival was 18.0 months. If LDH was higher than 300 U/l, overall survival was reduced to 12 months. In cases with extensive disease, overall survival was significantly lower in patients with elevated LDH serum levels with an additional reduction in overall survival in patients with LDH levels above 300 U/l. (7.0 vs. 12.0 months, p = <0.001). Multivariate Cox regression analyses revealed LDH levels to be an independent predictor of mortality after adjustment for age and Performance Status in LD and ED SCLC (HR 1.003, p = 0.017; HR 1.001, p = 0.002 respectively). However, categorizing LDH levels revealed no significant difference in LD SCLC.Conclusion: In our contemporary comprehensive patient population, LDH is proved to be a strong, independent predictive factor of median survival in patients with LD and ED SCLC.

Chronic respiratory disease and multimorbidity: Prevalence and impact in a general practice setting - Corrected Proof

S. O’Kelly, S.M. Smith, S. Lane, C. Teljeur, T. O’Dowd — 2010-08-17

Summary: Background: Multimorbidity is defined as two or more co-existing chronic conditions in an individual and is common in general practice. It is associated with poorer outcomes for patients. This study aimed to establish the prevalence of multimorbidity in patients with chronic respiratory disease in general practice and to describe its impact on health service use.Methods: Cross-sectional study based in general practice in Dublin. Drug and disease code searches were performed to identify adult patients with a diagnosis of chronic respiratory disease. Medical records were reviewed for chronic respiratory diagnosis, other chronic conditions, demographic characteristics, General Practitioner (GP) and practice nurse utilisation rates, and numbers of medications.Results: In a general practice population of 16,946 patients 3.9% had chronic respiratory disease and 60% of these had one or more co-existing chronic condition(s). GP and practice nurse utilisation rates, and number of medications were significantly higher among those with multimorbidity compared with those with respiratory disease alone. Multivariate analysis showed that increasing age and low socio-economic status were significantly associated with multimorbidity.Conclusion: The majority of patients with chronic respiratory disease have multimorbidity. Clinical guidelines based on single disease entities and outcomes are not as easy to implement and may not be as effective in this group.

Phenotypic differences between asymptomatic airway hyperresponsiveness and remission of asthma - Corrected Proof

Takahiro Yoshikawa, Hiroshi Kanazawa — 2010-08-13

Summary: Background: The present study aimed to illustrate differences in characteristics and perception of dyspnea between young atopic adults who have no history of asthma (never-asthmatics) with or without asymptomatic airway hyperresponsiveness (AHR) and those who had childhood asthma and consider themselves to be grown out of the disease (past-asthmatics).Methods: Blood parameters, lung function and methacholine PC20 were measured in 88 never-asthmatics and 24 past-asthmatics. A perception score of dyspnea at 20% fall in FEV1 (PS20) was obtained by interpolation of the two last points on the perception (modified Borg scale)/fall in FEV1 curve during methacholine challenge.Results: Thirty-one of 88 never-asthmatics and eighteen of 24 past-asthmatics exhibited AHR (PC20 was <8 mg/ml). Higher levels of specific IgE to house dust mite in past-asthmatics were observed than never-asthmatics with and without AHR. Mean values of FEV1 and FEF25–75 (%predicted) were significantly lower in past-asthmatics than never-asthmatics without AHR, and the values in never-asthmatics with AHR were intermediate between never-asthmatics without AHR and past-asthmatics. PC20 was not significantly different between past-asthmatics and never-asthmatics with AHR. Of particular interest was that PS20 was significantly lower in never-asthmatics with AHR compared with past-asthmatics.Conclusion: The present findings suggest the possibilities that presence or absence of past history of outgrow of childhood asthma might be associated with airway narrowing, sensitization to house dust mite and perception of dyspnea in young asymptomatic adults with atopy and AHR.

Three-year dispensing patterns with long-acting inhaled drugs in COPD: A database analysis - Corrected Proof

2010-08-12

Summary: Background: Long-acting muscarinic antagonists (LAMA), long-acting β2-agonists (LABA) and fixed dose combinations (FDC) of inhaled corticosteroids (ICS) and LABA are used as inhaled maintenance therapies for COPD.Objective: To estimate persistence rates from dispensing patterns of long-acting inhaled drugs for COPD.Methods: From the PHARMO-database, COPD patients starting LAMA, LABA or LABA-ICS FDC between 2002 and 2006 were selected. Persistence with the initial as well as with any long-acting inhaled drug was determined, defined as time between start and stop of initial/any therapy, allowing ≤60-days gaps between refills. For patients who did not continue to receive dispensings of the initial therapy for at least one year, the first change in therapy was determined.Results: The study included 2201 LAMA, 1201 LABA and 4146 LABA-ICS FDC users. Persistence rates with initial therapy alone at 1, 2, and 3 years were 25%, 14%, 8% for LAMA, 21%, 10%, 6% for LABA and 27%, 14%, 8% for LABA-ICS FDC. Of patients who did not persist with LAMA alone for one year, 15% added and 13% switched therapy (both mostly LABA-ICS FDC). Of patients not persisting with LABA alone, 9% added therapy (mostly LAMA) and 31% switched therapy (mostly to LABA-ICS FDC). In patients not persisting with LABA-ICS FDC, add-on and switch occurred equally frequent (11%, mostly LAMA). Persistence rates with any long-acting drug at 1, 2 and 3 years were 36%, 23% and 17% respectively.Conclusion: Persistence with the initial as well as with any long-acting inhaled drug in COPD is low, with a substantial proportion of patients changing therapy.

Predictive factors for evaluation of response to fluticasone propionate/salmeterol combination in severe COPD - Corrected Proof

2010-08-12

Summary: Background: The predictive factors for treatment response in patients with severe chronic obstructive pulmonary disease (COPD) are unknown. We investigated predictive factors for response to fluticasone propionate/salmeterol (FSC) in severe COPD patients.Methods: This prospective, open-label, non-comparative study included 921 adult patients with severe COPD (baseline forced expiratory volume in 1 s (FEV1) <50% of predicted), a history of repeated exacerbations, and symptoms despite bronchodilator treatment. FSC (500 μg/50 μg) was delivered via an inhaler, twice a day, for 12 weeks. The primary efficacy endpoint was the response rate for inspiratory capacity (IC), FEV1, or quality of life (QoL), assessed with the Saint George’s respiratory questionnaire, at week 6 and week 12.Results: The overall response rate to FSC at 6 and 12 weeks was 79%. The corresponding rates for FEV1, IC, and QoL were 38%, 55%, and 62%, respectively. More than 40% of patients showed a response for IC and/or QoL without being responders for FEV1. Overall lung function and QoL were improved. FSC was well tolerated with a safety profile consistent with that observed previously.Conclusion: Nearly 80% of patients responded to FSC treatment in this real-life study. Improvements in IC and QoL at 12 weeks revealed a clinically relevant response in patients with no improvement in FEV1. IC reversibility to salbutamol before treatment might represent, better than FEV1, a prognostic factor of response to FSC in severe COPD. Moreover these tests are easy to perform routinely and in large numbers of patients.

Self-reported symptoms and bronchial hyperresponsiveness in elite cross-country skiers - Corrected Proof

Nikolai Stenfors — 2010-08-12

Summary: Introduction: Respiratory symptoms in relationship to exercise, bronchial hyperresponsiveness (BHR), and exercise-induced asthma (EIA) are very common in elite winter athletes. Symptom-based screening for BHR would facilitate selection of athletes with possible EIA.Objectives: The aim of the present study was to evaluate the diagnostic accuracy of self-reported symptoms as predictors of BHR in an unselected population of adult elite cross-country skiers.Methods: Forty-six Swedish adult skiers competing at national or international level were included. They had a mean (SD) training volume in the past 12 months of 593 (122) hours. Twenty-four subjects had previous physician-diagnosed asthma. The European Community Respiratory Health Survey questionnaire was used to evaluate the presence of respiratory symptoms. BHR was defined as bronchoconstriction to either eucapnic voluntary hyperventilation, dry powder mannitol or methacholine provocation.Results: The “classical” EIA symptom of shortness of breath post-exercise was reported by 17% of all skiers. Eight subjects (17%) had BHR. None of the self-reported respiratory symptoms had high positive predictive values. However, symptoms caused by grass or pollen had high negative predictive values.Discussion: EIA in elite winter athletes cannot accurately be based only on self-reported symptoms but requires verification with objective testing of BHR. Bronchoprovocation of elite winter athletes reporting respiratory symptoms in rest or because of exercise will probably reveal a high proportion of athletes without BHR.Clinical trial: EUDRA-CT number 2006-005822-21.

The effect of challenge method on methacholine-induced changes in sensitivity and air trapping - Corrected Proof

2010-08-09

Summary: Background: The methacholine challenge test performed with the tidal breathing method induces a greater fall in FEV1 than the dosimeter method; however, the effect of the challenge method on methacholine-induced fall in FVC has not been investigated.Objective: To determine the influence of the challenge method on methacholine-induced changes in FEV1 and FVC.Methods: Airway responsiveness to methacholine was determined by dosimeter method and tidal breathing method in 37 subjects with suspected asthma. The dosimeter was modified to deliver an identical volume to that obtained with the tidal breathing method and the same nebulizer model was used for the two challenges. The response was expressed by the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) and by the percent fall in FVC at the PC20 value relative to FVC after saline inhalation.Results: The PC20 values obtained with the tidal breathing method and the dosimeter method were similar, with geometric mean values of 3.15 (95%CI, 1.85–5.34 mg/mL) and 2.51 (1.37–4.61 mg/mL, P = 0.092), respectively. The percent fall in FVC at the PC20 value obtained with the dosimeter was significantly greater than that obtained with the tidal breathing method, with mean values of 11.8 (95%CI, 10.0–13.5%) and 9.4 (95%CI, 8.1–10.8, P = 0.002), respectively.Conclusions: Differences in methacholine PC20 values obtained with the two challenge methods recommended in guidelines may be overcome by introducing some technical modifications in the dosimeter method. However, the technical factors that affect methacholine sensitivity and air trapping are at least partially different.

Exercise but not mannitol provocation increases urinary Clara cell protein (CC16) in elite swimmers - Corrected Proof

Kerstin Romberg, Leif Bjermer, Ellen Tufvesson — 2010-08-09

Summary: Elite swimmers have an increased risk of developing asthma, and exposure to chloramine is believed to be an important trigger factor. The aim of the present study was to explore pathophysiological mechanisms behind induced bronchoconstriction in swimmers exposed to chloramine, before and after swim exercise provocation as well as mannitol provocation. Urinary Clara cell protein (CC16) was used as a possible marker for epithelial stress.101 elite aspiring swim athletes were investigated and urinary samples were collected before and 1 h after completed exercise and mannitol challenge. CC16, 11β-prostaglandin (PG)F2α and leukotriene E4 (LTE4) were measured.Urinary levels of CC16 were clearly increased after exercise challenge, while no reaction was seen after mannitol challenge. Similar to CC16, the level of 11β-PGF2α was increased after exercise challenge, but not after mannitol challenge, while LTE4 was reduced after exercise. There was no significant difference in urinary response between those with a negative compared to positive challenge, but a tendency of increased baseline levels of 11β-PGF2α and LTE4 in individuals with a positive mannitol challenge.The uniform increase of CC16 after swim exercise indicates that CC16 is of importance in epithelial stress, and may as such be an important pathogenic factor behind asthma development in swimmers. The changes seen in urinary levels of 11β-PGF2α and LTE4 indicate a pathophysiological role in both mannitol and exercise challenge.

CT lung densitometry in young adults with alpha-1-antitrypsin deficiency - Corrected Proof

2010-08-02

Summary: Background: Severe (PiZZ) and moderate (PiSZ) alpha-1-antitrypsin (AAT) deficiency predispose to lung emphysema, especially in smokers. We hypothesized that multi-slice computed tomography (CT) might be superior to pulmonary function tests (PFT) to detect lung emphysema in AAT-deficient individuals at the age of 32 years.Methods: A subgroup of PiZZ and PiSZ individuals identified during the Swedish newborn screening programme in 1972–74 underwent multi-slice CT and PFT at the age of 32 years. From the CT scans the percentile density at 15% (PD15) and the relative area below –910 Hounsfield Units (RA−910 HU) were calculated. The results of PFT and CT were compared between the AAT-deficient individuals and an age-matched control group.Results: Twenty-five PiZZ, 11 PiSZ and 17 PiMM individuals participated in the study. All Pi subgroups had normal lung function. The mean PD15 was 81 (SD 22) g/L in the PiZZ individuals, 96 (SD 35) g/L in the PiSZ individuals and 79 (SD 17) g/L in the PiMM individuals (ns), and the RA-910 were 30 (SD 18)%, 24 (SD 20)%, and 32 (SD 18)%, respectively (ns). For the never-smoker subgroups, in the PiZZ (n = 23), PiSZ (n = 8) and PiMM (n = 12), the mean PD15 were 95 (SD 35) g/L, 81 (SD 22) g/L, and 75 (SD 12) g/L, respectively (ns). PD15 was significantly correlated to CT derived lung size (r = −0.72; p < 0.001).Conclusions: CT densitometry revealed no signs of emphysema and no differences between the AAT-deficient individuals identified by neonatal screening and age-matched control subjects.

A retrospective analysis of practice patterns in the management of acute asthma attack across Turkey - Corrected Proof

Haluk Türktaş, Sevim Bavbek, Zeynep Mısırlıgil, Bilun Gemicioğlu, Dilşad Mungan — 2010-08-02

Summary: Objective: To evaluate patient characteristics and practice patterns in the management of acute asthma attack at tertiary care centers across Turkey.Methods: A total of 294 patients (mean age: 50.4 ± 15.1 years; females: 80.3%) diagnosed with persistent asthma were included in this retrospective study upon their admission to the hospital with an acute asthma attack. Patient demographics, asthma control level, asthma attack severity and the management of the attack were evaluated.Results: There was no influence of gender on asthma control and attack severity. In 57.5% of the patients, asthma attack was moderate. Most patients (78.9%) were hospitalized with longer duration evident in the severe attack. Spirometry and chest X-Ray were the most frequent tests (85.4%), while steroids (72.0% parenteral; 29.0% oral) and short-acting beta-agonists (SABA) + anticholinergics (45.5%) were the main drugs of choice in the attack management. Attack severity and pre-attack asthma control level was significantly correlated (p < 0.001). Pre-attack asthma was uncontrolled in 42.6% of the patients with severe attack. Most of the patients were on combination of more than one (two in 38.7% and 3–4 in 31.2%) controller drugs before the attack.Conclusion: Providing country specific data on practice patterns in the management of acute asthma attack in a representative cohort in Turkey, prescription of steroids and SABA + anticholinergics as the main drugs of choice was in line with guidelines while the significant relation of pre-attack asthma control to risk/severity of asthma attack and rate/duration of hospitalization seem to be the leading results of the present study.

A longitudinal study of serial BODE indices in predicting mortality and readmissions for COPD - Corrected Proof

2010-07-23

Summary: Introduction: BODE index comprises Body mass index, Obstruction of the airway [FEV1], Dyspnoea score [modified Medical Research Council questionnaire] and Exercise capacity [6 min walk test]. This study assessed the role of serial changes in BODE index in predicting mortality and readmissions of COPD patients.Methods: A prospective cohort study involving 243(208males) COPD patients hospitalized for acute exacerbations of COPD [AECOPD]. BODE index was assessed at 6 weeks(baseline), 6, 12, 18 and 24 months post hospital discharge. Mortality and readmissions in the subsequent 3 years were recorded. All the patients were managed by usual care without additional intervention.Results: The mean (SD) age and FEV1% predicted were 74.2(7.8) yrs and 51.7(21.6)% respectively. Over the 3 years, 25.1% died whereas 76.5% had at least 1 readmission for AECOPD. Baseline BODE index was predictive of both the survival and readmissions to hospital for AECOPD by Cox regression analysis (p 1point), no change, and decreased in BODE (>1point) index respectively. Serial changes in BODE index at 6 month was marginally associated with mortality, but not at 12-, 18- and 24-month. The 6-, 12- and 24-month BODE indices were predictive of the readmissions for AECOPD when compared to baseline.Conclusion: Baseline BODE index could predict both survival and readmissions for AECOPD, whereas serial BODE indices were not predictive of survival at 3 years. Single rather than serial measurements of BODE index is sufficient for prediction of survival and readmissions for patients treated with usual care.

Comparison of a network of primary care physicians and an open spirometry programme for COPD diagnosis - Corrected Proof

2010-07-22

Summary: Background: Early diagnosis of Chronic Obstructive Pulmonary Disease (COPD) remains the cornerstone for effective management. In this study we compared an open spirometry programme and a case-finding programme providing spirometry to high-risk subjects selected by primary care physicians.Methods: A network of primary care physicians was created after invitation and all participants received training on COPD and spirometry. The study team visited 12 primary care settings in each programme in a 1-year period. Spirometry was performed in all eligible participants. COPD diagnosis and classification was based on GOLD guidelines and evaluation by a chest physician.Results:: Patients with acceptable spirometry were evaluated (n = 201 in the case-finding and n = 905 in the open spirometry programme). The proportion of newly diagnosed COPD was 27.9% in the case-finding programme compared to 8.4% in the open spirometry programme (p < 0.0001). The numberneeded-to-screen (NNS) for a new diagnosis of COPD was 3.6 in the case-finding programme compared to 11.9 in the open spirometry programme. The majority of newly diagnosed patients were classified in GOLD stages I an II. The average cost for a new diagnosis of COPD was 173€ in the open spirometry programme and 102€ in the case-finding programme.Conclusions: A case-finding programme involving primary care physicians was more cost-effective for the identification of new cases of COPD compared to an open spirometry programme. The development of networks of primary care physicians with access to good quality spirometry and specialist consultation for early diagnosis of COPD is justified.

Sensitivity of lung clearance index and chest computed tomography in early cf lung disease - Corrected Proof

2010-07-16

Summary: It is widely accepted that CF lung disease starts before clinical symptoms become apparent or spirometry deteriorates. Computed chest tomography (CT) is the reference method for identifying structural changes in CF; however, radiation exposure limits its use as a monitoring tool. It has been suggested that the Lung Clearance Index (LCI) measured by Multiple Breath Washout (MBW) for assessing ventilation inhomogeneity is a more sensitive surrogate marker than spirometry allowing non-invasive monitoring of CF lung disease.The aim of this study was to prospectively investigate the diagnostic accuracy of the LCI in comparison to CT in CF patients with early lung disease and normal FEV1 (>80% pred.).MBW and ultra-low-dose CT were performed in 34 patients (6–26 years). LCI was abnormal in 76.5% subjects. LCI and CT correlated significantly in 82.3%. LCI was related to presence and extent of structural lung changes observed on CT with a sensitivity of 88%.Diagnostic accuracy of the LCI for detecting CF lung disease in patients with normal FEV1 was good when compared to CT. Results indicate that structural changes are unlikely if a normal LCI is measured. We speculate that serial measurements of the LCI for assessing ventilation inhomogeneity may help to identify early structural lung disease and help to reduce the individual cumulative radiation dose. The LCI may be a suitable surrogate marker for monitoring progression of CF lung disease and effect of treatment in both, clinical care and research settings.

Relationship between matrix production by bronchial fibroblasts and lung function and AHR in asthma - Corrected Proof

Lizbet Todorova, Leif Bjermer, Anna Miller-Larsson, Gunilla Westergren-Thorsson — 2010-07-16

Summary: The reasons for enhanced deposition of extracellular matrix in the airways of asthmatic patients and the subsequent consequences on lung function are uncertain. Here, we investigated the synthesis of procollagen I and proteoglycans, the activity of various metalloproteinases (MMPs) and the production of their inhibitor TIMP-1 in biopsy-derived bronchial fibroblasts from eight patients with stable mild-to-moderate asthma, and how they are related to patients’ lung function and airway hyperreactivity (AHR).Following 24-h fibroblast incubation in 0.4% serum, procollagen I carboxyterminal propeptide (PICP), TIMP-1 and MMP-1 in cell media were analysed by ELISA, MMP-2, MMP-3, MMP-9 by zymography and total proteoglycan production by [35S]-sulphate-incorporation/ion chromatography.Patients’ FEV1% predicted and methacholine log PD20 negatively correlated with PICP synthesized by patients’ bronchial fibroblasts (r = −0.74 and r = −0.71, respectively). PICP and proteoglycan amounts positively correlated (0.8 ≤ r ≤ 0.9) with MMP-2 and MMP-3 activity. A positive correlation (r = 0.75) was also found between proteoglycan production and TIMP-1. There was no correlation between MMP-9 activity and PICP or proteoglycan production. MMP-9 activity positively correlated with patients’ FEV1% predicted (r = 0.97) and methacholine log PD20 (r = 0.86), whereas negative associations (−0.6 ≤ r ≤ −0.7) were observed for MMP-2 and MMP-3.In stable mild-to-moderate asthma, increased procollagen I synthesis and activity of MMP-2 and MMP-3 in bronchial fibroblasts may negatively affect patients’ lung function and AHR. In contrast, MMP-9 activity was not associated with procollagen or proteoglycan production, or worsening of patients’ lung function and AHR. An enhanced production of procollagen I and proteoglycans might be a result of a negative feedback from their degradation by MMP-2 and MMP-3.

Omega-3 polyunsaturated fatty acids and bronchial inflammation in grass pollen allergy after allergen challenge - Corrected Proof

2010-07-16

Summary: Ratio: Asthma is a major public health problem, with bronchial inflammation as the therapeutic target. The role of dietary fish oil derived polyunsaturated fatty acids (PUFAs) in allergic inflammation is controversial. Most asthmatics suffer from mild disease and non-pharmacologic interventions are attractive. This study investigates the anti-inflammatory potential of nutritional PUFAs in an experimentally induced bronchial inflammation.Methods: We examined 38 grass pollen allergic asthmatics and 19 controls. History of dietary PUFA intake was compared with levels of PUFAs in erythrocyte membranes, and stratified according to low (25th quartile; Q25) and high (75th quartile; Q75) ratios of omega-3 (n-3) to omega-6 (n-6) PUFAs as a surrogate for anti-inflammatory (Q75) or proinflammatory (Q25) effects. Bronchial inflammation was simulated with one-step inhalation of grass pollen. Bronchial response (exhaled nitric monoxide, eNO as surrogate for inflammation, decrease of FEV1) was correlated with levels of PUFAs in erythrocyte membranes.Results: Ratios of n-3/n-6 PUFA were significantly lower in asthmatics than in healthy controls. Levels of eNO were significantly higher in Q25 asthmatics than in Q75 asthmatics (p = 0.040). There was a trend of higher bronchial hyperreactivity in Q25 asthmatics (median PD20 0.27 vs. 0.14; n.s.), induced by specific bronchial challenge with grass pollen (FEV1 decrease 16.7 vs. 23.1%; n.s.).Conclusion: When stratifying for erythrocyte membrane PUFA content as a surrogate for alimentary intake, we found mild effects on bronchial allergic inflammation. Future intervention studies with pharmacological PUFA doses appear suitable to clarify dietary PUFA role as an adjunctive intervention to the established treatment of asthma.ClinicalTrials.gov No. NCT00519740.

Periodontal health and quality of life in patients with chronic obstructive pulmonary disease - Corrected Proof

Xuan Zhou, Zuomin Wang, Yiqing Song, Jing Zhang, Chen Wang — 2010-07-14

Summary: Objective: To evaluate the association of periodontal health and parameters of quality of life assessed in 306 Chinese patients with chronic obstructive pulmonary disease (COPD).Methods: Periodontal status and respiratory function in 306 COPD patients were clinically evaluated and their quality of life was assessed using the standardized St George’s Respiratory Questionnaire (SGRQ).Results: The SGRQ scores were all significantly correlated with major lung function parameters (r2 = −0.37 to −0.28; all p < 0.0001) and Medical Research Council dyspnoea scale (r2 = 0.23 to 0.30; all p < 0.0001). The SGRQ scores also correlated with the 6-min walk test (r2 = −0.15 to −0.13; all p < 0.05). Of periodontal health parameters, missing tooth number and plaque index appeared to be related to the scores of quality of life. The age- and gender-adjusted Pearson’s correlation coefficients between missing teeth and total score, symptoms score, and activity score were 0.09, 0.12, and 0.12, respectively (all p < 0.05). The Pearson’s correlation coefficients between plaque index and symptoms score and activity score were 0.09 and 0.09 (p < 0.05). After adjusting for age, gender, body mass index, and smoking status, missing teeth remained significantly associated with symptom score (p = 0.030) and activity score (p = 0.033) while plaque index was significantly associated with symptom score (p = 0.007).Conclusions: Poor periodontal health as reflected by missing teeth and plaque index was significantly associated with lower quality of life in COPD patients. Our findings indicate the importance of promoting dental care in current public health strategies to improve the quality of life in COPD patients.

24-h bronchodilator efficacy of single doses of indacaterol in Japanese patients with asthma: A comparison with placebo and salmeterol - Corrected Proof

2010-07-12

Summary: Background: Indacaterol is a novel, inhaled once-daily ultra-long-acting beta-2 agonist under development as a fixed-dose combination with an inhaled corticosteroid (ICS) for asthma treatment. This study evaluated the 24-h bronchodilator efficacy of indacaterol in Japanese patients with asthma.Methods: Randomised, placebo-controlled, 5-period crossover study. Patients with persistent asthma (18–75 years, FEV1 50–85% predicted, ≥12% and 200 mL FEV1 reversibility) receiving ICS were randomised to double-blind single dose indacaterol 150, 300, or 600 μg or placebo, with open-label salmeterol 50 μg twice-daily for one day in the 5th period. Primary endpoint was FEV1AUC22–24h.Results: Of 41 randomised patients (48.8% male; mean age: 47.8 years), 39 completed. All indacaterol doses showed significantly higher FEV1AUC22–24h than placebo (P<0.001), with treatment–placebo differences of 180, 220, and 260mL for indacaterol 150, 300, and 600 μg, respectively (salmeterol–placebo difference 170mL; P < 0.001). For individual time-point FEV1, all indacaterol doses were superior to placebo from 5min to 24h post-dose (P < 0.001). Compared with salmeterol, all indacaterol doses were superior from 5 to 30min (P < 0.05); in addition indacaterol 300 μg and 600 μg were superior at a number of subsequent time points. Changes in safety parameters with indacaterol were similar to placebo. All indacaterol doses were well tolerated.Conclusion: Single dose indacaterol provided sustained 24-h bronchodilation with a faster onset of action than salmeterol and a good overall safety and tolerability profile in Japanese patients with asthma. These results are consistent with data from Caucasian populations.

Limited airway effects in mild asthmatics after exposure to air pollution in a road tunnel - Corrected Proof

2010-07-12

Summary: Ambient air pollution is a contributing factor to respiratory morbidity and mortality and asthmatics are a particularly vulnerable population. The aim of the study was to investigate whether acute exposure to traffic related air pollution in a road tunnel would increase bronchial responsiveness in mild asthmatics, and if this would be accompanied by increased measures of inflammatory markers in the airways assessed by nasal lavage (NAL) and induced sputum.Fourteen mild asthmatics (7 treated with inhaled corticosteroids) were exposed for 2 h in a road tunnel and a control environment, respectively, separated by at least 3 weeks. Symptoms and peak expiratory flow (PEF) were recorded. Seven hours following exposure sessions, subjects underwent measurements of fraction of exhaled nitric oxide (FENO), spirometry, and a bronchial provocation test. NAL, induced sputum and blood samples were collected.The median PM2.5 and PM10 levels during the exposure occasions in the road tunnel were 80 (range 41–93) μg/m3 and 183 (72–213) μg/m3 respectively. Irritative symptoms from the airways increased and PEF decreased after road tunnel exposure. Increased levels of IL-10, IL-12 and TNF-α were observed in NAL fluid from subjects without ongoing inhaled corticosteroid treatment. Forced expiratory volume in 1 s (FEV1) and the degree of bronchial responsiveness in asthmatics did not change significantly after tunnel exposure.We conclude that asthmatics exhibit increased symptoms, decreased PEF and signs of inflammatory response in the upper airways, after a 2 h road tunnel exposure. Our findings may further emphasize asthmatics as a vulnerable group to common air pollutants.

Efficacy and safety of three ciclesonide doses vs placebo in children with asthma: The rainbow study - Corrected Proof

2010-07-09

Summary: Objective: To evaluate the efficacy and safety of three doses of ciclesonide (with or without spacer) in children with persistent asthma.Patients and methods: This was a multicentre, double-blind, placebo-controlled, 12-week study of ciclesonide 40, 80 or 160 μg (once daily pm). Children (6–11 years) were randomised 1:1 to treatment via a metered dose inhaler (MDI) or MDI plus spacer. The primary variable was change from baseline in mean morning peak expiratory flow (PEF). Secondary variables included: time to first lack of efficacy (LOE), asthma control, forced expiratory volume in 1 s (FEV1), asthma symptom score and quality of life (QoL). Safety assessments included: adverse events (AEs), urinary cortisol excretion and body height.Results: In total, 1073 children received treatment. At endpoint, mean morning PEF significantly improved with all doses of ciclesonide vs. placebo. There was no difference over placebo in time to first LOE, but ciclesonide was superior to placebo on asthma control, symptom score, FEV1 and QoL. There were no differences between the spacer or non-spacer subgroups. The incidences of AEs were comparable between treatment groups (approximately 35%) and there were no between-group differences in body height or urinary cortisol.Conclusions: Ciclesonide 40–160 μg once daily is effective and well tolerated in children with persistent asthma; its efficacy and safety are unaffected by the use of a spacer.clinicaltrials.gov registration number: NCT00384189.

Walking abnormalities are associated with COPD: An investigation of the NHANES III dataset - Corrected Proof

2010-07-08

Summary: Research on the peripheral effects of COPD has focused on physiological and structural changes. However, different from muscular weakness or decreased physical activity, mechanical abnormalities of the muscular system, e.g. walking, have yet to be investigated. Our purpose was to utilize the National Health and Nutritional Examination Survey (NHANES) dataset to determine whether walking abnormalities are associated with COPD severity. To determine if walking abnormalities were independently associated with COPD severity, our analysis aimed to investigate the association of physical activity levels with COPD severity and with walking abnormalities. The NHANES III dataset that contains data for 31,000 persons that were collected from 1988 to 1994, was used to explore the association of COPD severity on gross walking abnormalities, i.e. limp, shuffle, etc. Logistic regression models were created using FEV1/FVC ratio, age, gender, BMI, and smoking status as predictors of walking abnormalities and physical activity in persons aged 40 to 90 years old. Results demonstrated a significant correlation between the presence of walking abnormalities and severe COPD (odds ratio: 1.97; 95% CI: 1.1 to 3.5). This suggests that disease severity can contribute to mechanical outcomes of patients with COPD. In addition, decreased physical activity levels were significantly associated with all COPD severity levels with the exception of mild COPD. The association between altered gait and COPD status may be due to the presence of physical inactivity that is present in patients with COPD. Future research directions should include investigating more closely the mechanical outcomes of persons with COPD.

Airflow limitation and airway dimensions assessed per bronchial generation in older asthmatics - Corrected Proof

2010-07-08

Summary: Background: Computed tomography (CT) has been used for non-invasive quantitative assessment of airway dimensions, potentially showing airway remodeling, in asthma. However, most studies have examined either only one airway or only airways in anatomically unidentified cross-sections. Using software capable of precisely identifying the generation of airways and measuring airway dimensions perpendicular to the long axis of airways, we examined, in older patients with stable asthma, how inter-subject variation in airway dimensions correlated among the 3rd to 6th generation of airways, and then examined relationships between airway dimensions of each generation and indices of airflow limitation.Methods: Subjects aged ≥55 years old comprised 59 asthmatic patients who underwent CT and pulmonary function tests on the same day. We measured airway wall area (WA%) and inner luminal area (Ai) from the 3rd to the 6th generation of eight bronchi in the right lung.Results: Excellent correlations were identified for both WA% and Ai among the generations (r = 0.744–0.930 for WA%) when we took the average of all measured bronchi per generation as a personal representative value. Significant correlations of airflow limitation indices with both WA% and Ai/BSA were found at each of the 3rd to 6th generations with similar correlation coefficients (WA% for FEV1 %predicted, r = −0.410 to −0.556).Conclusions: In older patients with stable asthma, airway wall thickening and narrowing might occur in a parallel manner through 3rd to 6th generation airways. Airway dimensions at these areas of airways may thus have significant and similar correlations with indices of airflow limitation.

Prevalence and potential determinants of exertional dyspnea after acute pulmonary embolism - Corrected Proof

2010-07-05

Summary: Background: The exact prevalence and etiology of exertional dyspnea in the clinical course of acute pulmonary embolism (PE) have not yet been established.Methods: A large cohort of consecutive patients diagnosed with acute PE was subjected to a dyspnea questionnaire and invited for cardiopulmonary work-up including the 6-min walk test, spirometry and echocardiography. The prevalence, severity, determinants and underlying diseases of exertional dyspnea were evaluated.Results: Of the registered 877 patients, 259 (30%) had died and 11 (1.3%) were excluded for geographical reasons. From the remaining 607 patients, 217 reported exertional dyspnea (36%; 95% CI 32–40%) 3.6 ± 1.7 years after the PE. In 76% this dyspnea had developed or worsened after the acute PE. 421 patients completed the cardiopulmonary work-up. Cardiopulmonary comorbidity (OR 12; 95% CI 6.5–20), advanced age (OR 1.02 per year; 95% CI 1.01–1.03), higher BMI (OR 1.06 per kg/m2; 95% CI 1.01–1.1) and a smoking history (OR 1.6; 95% CI 1.02–2.6) were identified as independent predictors of exertional dyspnea. A pre-defined dyspnea explaining diagnosis could be established in all patients with exertional dyspnea. In only 4 patients, this diagnosis was directly correlated to the acute PE. Increased severity of dyspnea was associated with decreased exercise performance (p < 0.001) and a higher number of dyspnea-related diagnoses (p < 0.001).Conclusion: Exertional dyspnea is a frequent symptom in the long term clinical course of acute PE. More severe dyspnea results in decreased exercise capacity and increased burden of cardiopulmonary comorbidity. This dyspnea is likely to be unrelated to the past thromboembolic event in the vast majority of patients.

Clinical characteristics of health care-associated pneumonia in a Korean teaching hospital - Corrected Proof

2010-07-05

Summary: Background: Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. ATS/IDSA guidelines state that all patients with HCAP should receive empirical therapy directed at multidrug-resistant pathogens. However, recent data from other countries have reported a different picture of HCAP.Methods: We conducted a retrospective observational study of patients with HCAP and CAP who were hospitalized through the emergency department in January–December 2008 at Samsung Medical Center, Seoul, Korea, and compared clinical characteristics, severity, distribution of pathogen, and outcomes.Results: In total, 345 patients hospitalized with pneumonia were eligible, 182 (52.8%) with HCAP and 163 (47.2%) with CAP. Patients with HCAP had greater comorbidity and higher Pneumonia Severity Index (PSI) score (P < 0.001). Although Streptococcus pneumoniae was the most frequently isolated pathogen in HCAP and CAP patients, the occurrence of potentially drug-resistant pathogens (29.3% vs. 13.0%; P = 0.044) and inappropriate initial antimicrobial treatment (24.6% vs. 8.7%; P = 0.032) were significantly higher in HCAP patients. Patients with HCAP had a longer duration of hospital stay (13 [8–18] vs. 8 [6–12] days; P < 0.001), and higher in-hospital mortality (19.2% vs. 7.4%; P = 0.001). In a multiple logistic regression analysis, however, in-hospital mortality was independently associated with higher PSI class (OR 2.82, 95% CI 1.19–6.70) and ICU admission (OR 15.37, 95% CI 3.58–66.05).Conclusions: Severity of illness, rather than type of pneumonia, was the main predicting factor for in-hospital mortality among patients with pneumonia hospitalized through the emergency department.

Increased use of inhaled corticosteroids among young Danish adult asthmatics: An observational study - Corrected Proof

2010-07-02

Summary: Objective: This population-based longitudinal study aimed to investigate trends in use of inhaled corticosteroids (ICS) and determinants of ICS use in young Danish adults with asthma.Methods: 106 757 users, aged 18–44 years, of anti-asthmatic drugs were identified in the Danish Register of Medical Product Statistics during 1997–2006. One year prevalences of ICS use were calculated in categories of gender, age, and annual consumption of inhaled beta-2-agonists (IBA) in defined daily doses (DDD) per year. Determinants of ICS use were estimated by logistic regression models.Results: The one year prevalence of ICS use was constant, approximately 64%, during 1997–2000. An annual increase was observed from 67% in 2001 to 77% in 2006. This trend also existed when stratifying on gender, age and IBA use. Using 1997 as baseline, the adjusted odds ratios (ORs) of ICS use in 2000 was 0.98 (95% CI 0.96–1.01) compared to 1.12 (95% CI 1.09–1.15) in 2001, and 1.81 (95% CI 1.75–1.87) in 2006. Other determinants of high ICS use were female gender, young age, and high annual IBA consumption. Among those using at least 400 DDD of IBA per year (corresponding to 4.4 powder inhalations daily), nearly 20% had no ICS prescriptions in 2006.Conclusion: Treatment with ICS among young Danish adult asthmatics has increased since 2001. This apparent improvement was associated with the introduction of fixed dose combination inhalers with ICS and inhaled long-acting beta-2-agonists. However, there is still room for improvement.

Utility of high-resolution computed tomography and BAL in cryptogenic organizing pneumonia - Corrected Proof

2010-07-01

Summary: Background: Cryptogenic organizing pneumonia (COP) is a rare disease, and its diagnosis requires histological confirmation. The objective of our study was to describe the findings of the thoracic high-resolution computed tomography (HR-CT) and bronchoalveolar lavage (BAL) in patients with confirmed COP and evaluate the complementary diagnostic use of BAL and thoracic HR-CT.Methods: Patients recorded in the registry of interstitial pulmonary diseases between 1991 and 2008 were located and the COP patients selected.Results: We identified 21 patients with histological confirmation of COP. The median age was 58.0 ± 15.9 years, and 61.9% of patients were female. The most frequent thoracic HR-CT profile was patchy infiltrate (71.4%), followed by parenchymatous consolidation (42.9%). The most frequent BAL profile was mixed alveolitis (62%) with lymphocyte predominance, a CD4/CD8 index of 0.4 and foamy macrophages. The effectiveness of transbronchial biopsy was 66.6%. The diagnostic utility of Poletti’s BAL criteria gives us a specificity of 88.8%, although the sensitivity obtained was low. The specificity of certain HR-CT profiles is 99%. In addition, we observed a complementary use of the HR-CT and the BAL.Conclusions: The imaging findings and BAL could be useful for patients with appropriate clinical presentation and for those whose transbronchial biopsy is negative or for whom a confirmatory biopsy cannot be performed.

Obesity, high-sensitive C-reactive protein and snoring in older Chinese: The Guangzhou Biobank Cohort Study - Corrected Proof

2010-06-29

Summary: Background: abitual snoring and elevated high-sensitive C-reactive protein (HsCRP) have both been associated with increased risk of cardiovascular disease. However, snoring and HsCRP are elevated in obese states which may thus be the primary determinant of both. We therefore investigated whether snoring may mediate the increased vascular risk directly through increased inflammation as indicated by HsCRP levels or if other determinants predominated in a large older Chinese population.Methods: A total of 2508 males and 5709 females aged 50–85 years received a medical check-up including measurement of blood pressure, obesity indices, fasting total, LDL-, HDL-cholesterol, triglycerides, glucose and HsCRP. Information on self-reported snoring status was collected by standardized interview.Results: The age-adjusted geometric mean HsCRP concentrations increased significantly with higher snoring frequency in both genders (linear trend, p=0.02 for men and p<0.001 for women), but the association was no longer significant after controlling for waist and BMI. Furthermore, HsCRP levels were not significantly associated with snoring frequency groups stratified by BMI/waist quintiles in both genders, except for the 4th waist quintile in men. No interaction was observed between snoring and BMI/waist on HsCRP levels. The multivariate analysis showed that, in both genders, obesity, but not HsCRP, was associated with snoring.Conclusions: Our results showed that snoring frequency did not have an independent effect on inflammation after adjusting for adiposity, and may thus contribute to vascular disease through alternative mechanisms.

Gender and skeletal muscle characteristics in subjects with chronic obstructive pulmonary disease - Corrected Proof

2010-06-28

Summary: Background: The influence of gender in the clinical expression of COPD has received important attention. Limited information exists regarding gender differences in the skeletal muscle characteristics in COPD subjects. The present study was aimed to determine the differences in the skeletal muscle characteristics in men and women with and without COPD.Methods: For comparison we studied 24 female (61 ± 9 years) and 30 male (65 ± 8 years) COPD patients with similar disease severity. In addition healthy subjects, 17 women (58 ± 8 years), and 9 men (57 ± 8 years) were studied. Pulmonary function, health status, six minute walk distance test (6MWD) and vastus lateralis muscle biopsy were assessed. Fiber type proportion, fiber type cross sectional area (CSA), capillary counts, and activity of citrate synthase (CS), 3-hydroxyacyl-CoA-dehydrogenase (HAD) and lactate-dehydrogenase (LDH) were determined.Results: Pulmonary function, health status and 6MWD were similar in male and female COPD patients. Fiber type distribution was similar between women (I = 42 ± 9%, IIA = 39 ± 13%, IIX = 19 ± 7%) and men (I = 39 ± 13%, IIA = 38 ± 9%, IIX = 29 ± 10%) with COPD, as well as CSA, capillarity and enzymes (CS 8.59 ± 1.6 vs.9.74 ± 2.6, HAD 9.03 ± 1.9 vs. 9.84 ± 2.5, LDH 124 ± 48 vs. 151 ± 68 μmol min−1 g−1). In normal subjects a decrease in type IIX fibers CSA was found in women compared with men (3703 ± 1478 vs. 5426 ± 1386 μm2, respectively).Conclusions: Female and male with COPD have similar skeletal muscle characteristics; it is possible that the disease blurs the gender differences. On the other hand, there seems to be fewer differences in muscle characteristics between older men and women, perhaps due to lower male testosterone levels and physical inactivity.

Difference between patient-reported side effects of ciclesonide versus fluticasone propionate - Corrected Proof

2010-06-28

Summary: Rationale: Patient-reported outcomes provide new insights into the dynamics of asthma management. Further to asthma control and quality of life, self-reported side effects of treatment can be assessed with the validated Inhaled Corticosteroid Questionnaire (ICQ).Objectives: To compare patient-reported side effects between the inhaled corticosteroids ciclesonide and fluticasone propionate.Methods: Patients with moderate or moderate-to-severe asthma, pre-treated with a constant dose and type of medication, were randomized in three separate studies: 1) once daily ciclesonide 320 μg (n = 234) or twice daily fluticasone propionate 200 μg (n = 240); 2) twice daily ciclesonide 320 μg (n = 255) or twice daily fluticasone propionate 375 μg (n = 273); and 3) twice daily ciclesonide 320 μg (n = 259) or twice daily fluticasone propionate 500 μg (n = 244). Patients rated the side effect questions of the 15 domain ICQ on a 7-point Likert scale (0 = not at all, 6 = a very great deal) during scheduled visits.Results: The majority of side effect scores remained similar with ciclesonide but worsened statistically significantly with fluticasone propionate from baseline to the end of the study in within-treatment analyses. In between-treatment analyses of studies 1 and 3 ciclesonide significantly improved total side effect scores (p < 0.025) and 14 out of 30 individual local and systemic domain scores (p < 0.025) compared with fluticasone propionate. In Study 2, although ciclesonide improved the majority of scores compared with fluticasone propionate only ‘oropharyngeal itching’ reached statistical significance (p < 0.025, one-sided).Conclusion: Patient-perceived side effects differ depending on the type of inhaled corticosteroids used. Patients with moderate-to-severe asthma report less intense side effects assessed with ICQ with ciclesonide than with fluticasone propionate.Clinical trial registration: The reported trials were completed before July 1 2005 and, therefore, are not registered.

Beneficial effect of inhaled mannitol and cough in asthmatics with mucociliary dysfunction - Corrected Proof

Evangelia Daviskas, Sandra D. Anderson, Stefan Eberl, Iven H. Young — 2010-06-24

Summary: Asthmatics with overproduction of mucus that is viscous and sticky have impaired mucociliary clearance (MCC) leading to mucus plugs, and airway obstruction. Inhaled mannitol improves mucus clearance in other hypersecretory diseases. This study investigated the effect of mannitol and cough in asthmatics with mucociliary dysfunction.Seven stable asthmatics, age 52 ± 20 yr, lifelong non-smokers, without the diagnosis of bronchiectasis, with chronic cough and sputum production, treated with inhaled corticosteroids participated in the study. MCC and cough clearance (CC) was measured on 4 visits: at baseline (no cough or mannitol), with mannitol (240 and 480 mg) and cough control (no mannitol) over total 90 min using a radioaerosol technique and imaging with a gamma camera. Cough clearance was assessed after MCC by asking subjects to cough 100 times over 30 min. Premedication with eformoterol (12 μg) on all visits protected all subjects from bronchoconstriction (fall in FEV1 > 15%) in response to mannitol.Mean (±SD) clearance over 60 min increased from 5.5 ± 5.6% at baseline and 7.3 ± 6.6% with cough control to 19.5 ± 14.6% and 26.4 ± 11.5% with 240 mg (p 0.05). Mannitol improved clearance in all lung regions (p < 0.005).In conclusion, mannitol improved both mucociliary and cough clearance in asthmatics with mucociliary dysfunction and ineffective cough clearance.Clinical Trial registered with www.anzctr.org.au; Number ACTRN 12609001066279.aspx.

Respiratory muscle strength in pregnancy - Corrected Proof

2010-06-24

Summary: Background: Muscle respiratory strength studies during pregnancy are very scarce. The aim of this paper is to describe maximum inspiratory (PImax) and expiratory (PEmax) mean pressure values in women during their first pregnancy and to determine the relationship between the anthropometric, morphologic and physiologic variables of these pressures.Methods: One hundred and twenty women (120) primigravidas were studied from the 5th to 40th gestational week, ages ranging from 20 to 29 years old, euthrophic and with low risk pregnancies.Results: PImax and PEmax mean values were 88.5 ± 16.52 cmH2O and 99.76 ± 18.19 cmH2O respectively. There was no association between gestational age and PImax (r = −0.06; p = 0.49) or PEmax (r = −0.11; p = 0.22). There was also no difference between PImax and PEmax during pregnancy trimesters and no correlation between pregnancy age and the pressures in each trimester. Height was the only anthropometric variable indicating a significant PImax (r = 0.20; p = 0.02) association. Fundal uterus height and inter-recti abdominis distance were not associated to respiratory pressure values. PEmax is not associated with the group of predictor variables (p = 0.127) and PImax demonstrated an independent association with height and dyspnea during physical exertion reflected by the following equation: PImax = 0.6 + 57.9 height – 1.68 dyspnea under effort. The present study suggests that inspiratory and expiratory maximum pressure values are not altered during different stages of pregnancy, however longitudinal studies are needed to assess changes over time.

Predictive accuracy of the pneumonia severity index vs CRB-65 for time to clinical stability: Results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study - Corrected Proof

2010-06-24

Summary: Background: The Pneumonia Severity Index (PSI) and CRB-65 are scores used to predict mortality in patients with community-acquired pneumonia (CAP). It is unknown how well either score predicts time to clinical stability in hospitalized patients with CAP. Thus, it is also not known which score predicts time to clinical stability better.Methods: A secondary analysis of 3087 patients from the Community-Acquired Pneumonia Organization (CAPO) database was performed. Time-dependent receiver-operator characteristic (ROC) curves for time to clinical stability were calculated for the PSI and CRB-65 scores at day seven of hospitalization. Secondary outcomes were to assess the relationship of the PSI and CRB-65 to in-hospital mortality and length of stay (LOS). ROC curves for LOS and mortality were calculated.Results: The area under the ROC curve (AUC) for time to clinical stability by day seven was 0.638 (95% CI 0.613, 0.660) when using the PSI, and 0.647 (95% CI 0.619, 0.670) while using the CRB-65. The difference in AUC values was not statistically significant (95% CI for difference of −0.03 to 0.01). However, the difference in the AUC values for discharge within 14 days (0.651 for PSI vs 0.63 for CRB-65, 95% CI for difference 0.001–0.049), and 28-day in-hospital mortality (0.738 for PSI vs 0.69 for CRB-65, 95% CI for difference 0.02–0.082) were both statistically significant.Conclusions: This study demonstrates a moderate ability of both the PSI and CRB-65 scores to predict time to clinical stability, and found that the predictive accuracy of the PSI was equivalent to that of the CRB-65 for this outcome.

Genetic influences on chronic obstructive pulmonary disease – A twin study - Corrected Proof

2010-06-14

Summary: Background: Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted.Methods: Hospital discharge diagnoses data on COPD were analysed in 22,422 Danish twin pairs, 20–71 years of age. The analyses were replicated in a population of 27,668 Swedish twin pairs, 45–108 years of age. A Cox-regression model was applied to the discordant time from the age at first hospital admission for COPD in the co-twin of an affected twin. Latent factor models were used to estimate genetic and environmental effects.Results: The probandwise concordance rate for COPD was higher in monozygotic (MZ) than in dizygotic (DZ) twins, 0.19 vs. 0.07 (p = 0.08) in the Danish population, and 0.20 vs. 0.08 (p = 0.006) in the Swedish population.After adjusting for sex, smoking and age at first hospital admission the risk of developing COPD in the co-twin of an affected twin was higher in MZ than in DZ twins, with hazards ratio 4.3 (95% confidence interval 1.2–15.8, p = 0.03) in Danish twins and 3.4 (1.5–7.7, p = 0.004) in Swedish twins. According to the most parsimonious model, additive genetic factors explained 63% (46–77%) of the individual COPD-susceptibility in the Danish population and 61% (48–72%) in the Swedish population.Conclusion: The susceptibility to develop severe COPD, as defined by hospitalizations, is strongly influenced by genetic factors. Approximately 60% of the individual susceptibility can be explained by genetic factors.

Categorization and impact of pulmonary hypertension in patients with advanced COPD - Corrected Proof

2010-06-14

Summary: Introduction: The functional significance of pulmonary hypertension (PH) in COPD is unclear. The purpose of the study was to define the prevalence, severity and associated functional impact of PH in patients with severe COPD listed for lung transplant.Methods: A retrospective review of the Organ Procurement and Tissue Network (OPTN) database between 1997 and 2006 for patients with the primary diagnosis of COPD. Baseline demographics, hemodynamics, pulmonary function tests, six minute walk distance test (6MWD) and pre-transplant survival data was analyzed.Results: 4930 patients with COPD had evaluable right heart catheterization data (RHC). PH was present in 30.4%, with pulmonary venous hypertension (PVH) accounting for an additional 17.2% of patients. Patients with pulmonary hypertension walked an average of 28 m less than those with normal hemodynamics. Normal hemodynamics group: 261 ± 104 m, PH; 238 ± 106 m (p < 0.01), PVH: 228 ± 104 m (p < 0.05). In a multivariable analysis, the mean pulmonary artery pressure (β = −1.33; p = 0.01) was an independent predictor of a reduced 6MWD, as were forced vital capacity (β = 1.48; p < 0.001) and patient age (β = −1.91; p < 0.001). Both PH (HR 1.23 95%CI [1.01–1.50]) and PVH (HR 1.35 95%CI [1.11–1.65]) were shown to be independent risk factors for mortality on the waiting list, even after adjustment for age sex, race, BMI, lung function, severity of illness and diabetes (PH: HR 1.27; 95%CI [1.04–1.55], PVH: HR 1.40; 95%CI [1.13–1.73]).Conclusion: PH is common in advanced COPD and is associated with functional impairment and an increased mortality risk. Stratification by RHC determined pulmonary hemodynamics appears important in distinguishing distinct clinical phenotypes.

Airway dimensions in COPD: Relationships with clinical variables - Corrected Proof

2010-06-11

Summary: Background: COPD patients have varying degrees of airways disease and emphysema. CT scanning can differentiate these pathological subtypes. We evaluated airway dimensions and emphysema severity with low dose CT scanning in COPD patients to determine relationships with clinical features of the disease.Methods: Fifty six patients with COPD had a low dose thoracic CT scan. Airways were analysed using novel software as either proximal (1st and 2nd generation) or distal (3rd to 6th generation); the extent of emphysema was assessed as the percentage of pixels less than −950 Hounsfield units. CT measures were related to clinical features of COPD.Results: Thicker walls in the proximal airways were associated with clinical features that may represent a bronchitic phenotype (MRC Bronchitis Score; β = 0.20, p = 0.003, Frequent Exacerbations; β = 0.14, p = 0.017, Total St George’s Score; β = 0.50, p = 0.001 and body mass index [BMI]; β = 0.26, p = 0.049); these associations were independent of emphysema. BMI was negatively correlated with the degree of emphysema (β = −0.41, p = 0.001). Airway wall thickness was negatively correlated with CT measured emphysema for both proximal and more distal airways (r = −0.30, p = 0.025 and r = −0.32, p = 0.015).Conclusions: CT measured airway dimensions are associated with several clinical measures of COPD; these are related to a bronchitic phenotype and the effect is independent of emphysema.

Reliability and validity of the clinical COPD questionniare and chronic respiratory questionnaire - Corrected Proof

2010-06-11

Summary: Background: Questionnaires are often used in assessing health-related quality of life in patients with chronic obstructive pulmonary disease (COPD). It is important that these questionnaires have good reliability, validity, and responsiveness. The aim of this study was to investigate and compare these properties in the disease specific Clinical COPD Questionnaire (CCQ) and the Chronic Respiratory Questionnaire self-reported (CRQ-SR).Methods: Two hundred ninety six participants with spirometry confirmed mild to moderate COPD were included in a smoking cessation trial. It was assumed that health-related quality of life would improve in participants who stopped smoking. The questionnaires were administered at baseline and at weeks 5, 26, and 52 after the target quit date.Results: At baseline, 292 (97%) participants returned the CCQ and 296 (100%) the CRQ-SR questionnaire. For both instruments, the internal consistency was good (Cronbach’s alpha >70%) as was the convergent validity with each other but not with spirometry. The CCQ was responsive to improvements in respiratory symptoms at both week 26 (−1.02, SD = 0.81) and 52 (−1.04, SD = 0.91) and in the total score at week 26 (−0.54, SD = 0.50) and 52 (−0.43, SD = 0.44). The mastery domain and the total score of the CRQ-SR were responsive at week 26 (1.14, SD = 0.82; 0.67, SD = 0.97 respectively) but not at week 52 (0.04, SD = 0.93; 0.38, SD = 0.57 respectively).Conclusion: Both the CCQ and CRQ-SR are equally reliable and valid. The long-term responsiveness of the CCQ is better. Both questionnaires can be used in future studies involving patients with mild to moderate COPD. However, when the follow-up exceeds 26 weeks, the CCQ is the recommended alternative.Netherlands Trial Register: ISRCTN 64481813.

Global muscle dysfunction as a risk factor of readmission to hospital due to COPD exacerbations. - Corrected Proof

2010-06-11

Summary: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients.Methods: A multicentre study was carried out in 121 COPD patients (92% males, 63 ± 11 yr, FEV1, 49 ± 17%pred). Assessments included anthropometrics, lung function, body composition using bioelectrical impedance analysis (BIA), and global muscle function (peripheral muscle (dominant and non-dominant hand grip strength, HGS), inspiratory (PImax), and expiratory (PEmax) muscle strength). GOLD stage, clinical status (stable vs. non-stable) and both current and past hospital admissions due to COPD exacerbations were included as covariates in the analyses.Results: Respiratory and peripheral muscle weakness were observed in all subsets of patients. Muscle weakness, was significantly associated with both current and past hospitalisations. Patients with history of multiple admissions showed increased global muscle weakness after adjusting by FEV1 (PEmax, OR = 6.8, p < 0.01; PImax, OR = 2.9, p < 0.05; HGSd, OR = 2.4, and HGSnd, OR = 2.6, p = 0.05). Moreover, a significant increase in both respiratory and peripheral muscle weakness, after adjusting by FEV1, was associated with current acute exacerbations.Conclusions: Muscle dysfunction, adjusted by GOLD stage, is associated with an increased risk of hospital admissions due to acute episodes of exacerbation of the disease. Current exacerbations further deteriorate muscle dysfunction

Epithelial apoptosis as a clinical marker in idiopathic interstitial pneumonia - Corrected Proof

2010-06-10

Summary: Backgrounds: Epithelial cell apoptosis plays an important role in the pathogenesis of idiopathic interstitial pneumonia (IIP).Methods: Serum levels of caspase-cleaved cytokeratin-18 (M30) were measured in 55 patients with IIP and 34 healthy controls using enzyme-linked immunosorbent assays. The IIP cases included usual interstitial pneumonia (UIP; n = 30), nonspecific interstitial pneumonia (NSIP; n = 15), and cryptogenic organizing pneumonia (COP; n = 10). The radiological scoring was performed based on high-resolution computed tomography (HRCT) findings.Results: Patients with IIP had higher serum M30 levels than did the control group (178.6 ± 91.5 vs. 113.7 ± 46.8 U/L, p < 0.05). Among IIP patients, COP patients had higher serum M30 levels than did UIP or NSIP patients (264.9 ± 132.7, 139.2 ± 49.7, and 201.2 ± 81.1 U/L, respectively; COP vs. UIP, p < 0.01). Serum M30 levels were negatively correlated with forced vital capacity (FVC; rs = −0.31), percent-predicted FVC (FVC%; rs = −0.38), and percent-predicted forced expiratory volume in 1 s (FEV1%; rs = −0.36). Serum M30 levels were correlated with radiological ground-glass opacity scores (rs = 0.61).Conclusion: The epithelial apoptosis marker serum level was correlated with IIP clinical status and is a potential marker to assess IIP.

The radiological patterns of interstitial change at an early phase: Over a 4-year follow-up - Corrected Proof

2010-06-10

Summary: Objectives: The identification of early phase interstitial changes may influence the understanding of idiopathic interstitial pneumonitis. This study aimed to clarify its radiological patterns and the association with smoking.Methods: The subjects underwent low-dose computed tomography to screen lung cancer. The selected subjects with interstitial changes were monitored for the precise morphology of interstitial changes using a high-resolution computed tomography (HRCT) scan. The subjects were classified into normal and abnormal HRCT subjects. The radiological findings on the HRCT scan, serum Klebs von der Lungen-6 (KL-6), surfactant protein (SP)-A, SP-D, pulmonary function, and computed tomography (CT) scores were analyzed. Abnormal HRCT subjects were classified based on the radiological patterns, and were followed-up over a 4-year period.Results: HRCT abnormalities suggesting interstitial changes were identified in 80 of 3079 subjects. Seven subjects with honeycombing and 14 with combined pulmonary fibrosis and emphysema (CPFE) were identified. The frequencies of sex (male) and smoking in the subjects with honeycombing was higher than that of other patterns. The smoking history and the levels of serum KL-6, SP-A, and SP-D in abnormal HRCT subjects were significantly higher than those in normal HRCT subjects. Thirty-two of 73 abnormal HRCT subjects showed a progression of the CT scores in a chest HRCT over a 4-year period. Eighteen abnormal HRCT current smokers were included in the progression of CT scores.Conclusions: HRCT patterns, excluding interlobular septal thickening, show the progression of CT scores. Smokers with CT abnormalities may have a tendency to demonstrate worsening interstitial changes.

Allergic rhinitis alone or with asthma is associated with an increased risk of sickness absences - Corrected Proof

2010-06-09

Summary: The aim of the study is to examine the risk of sickness absence in public sector employees with allergic rhinitis or asthma or both conditions combined.This is a prospective cohort study of 48 296 Finnish public sector employees. Data from self-reported rhinitis and asthma were obtained from survey responses given during either the 2000–2002 or 2004 periods. Follow-up data on sickness absences for the public sector employees surveyed were acquired from records kept by the employers.During the follow-up, mean sick leave days per year for respondents were 17.6 days for rhinitis alone, 23.8 days for asthma alone and 24.2 days for both conditions combined. Respondents with neither condition were absent for a mean of 14.5 days annually. The impact of asthma and rhinitis combined on the risk of sick leave days was marginal compared to asthma alone (RR 1.1; 95% CI 1.0–1.3). In the subgroup analysis (those with current asthma or allergy medication), the risk ratio for medically certified sickness absence (>3 days) was 2.0 (95% CI 1.9–2.2) for those with asthma and rhinitis combined.Rhinitis, asthma and both these conditions combined increased the risk of days off work.